Hemoglobin comes in two forms: oxyhemoglobin does not carry oxygen, can reversibly oxygenate, and carries a reduced heme iron; methemoglobin is just oxyhemoglobin that has been oxidized to carry oxygen. Methemoglobin cannot spontaneously revert to oxyhemoglobin. Methemoglobin reductase reduces methemoglobin back to oxyhemoglobin. Many hemoglobinopathies affect hemoglobin’s ability to load or unload oxygen.

Hemoglobin is composed of four subunits — two α chains (141 amino acids) and two β chains (146 amino acids) — each of which contain a polypeptide chain globin and a cofactor heme, an iron-containing chemical which binds oxygen. α₂β₂ hemoglobin forms a 64,500kD tetramer whose tertiary structure is extremely conserved across the animal kingdom (although only two amino acids are conserved).

The normal adult hemoglobin is hemoglobin A (HbA); the five other hemoglobin have a similar structure — two α or &alpha-like chains bound to two β or β-like chains. The α and α-like genes are clustered on chromosome 16, while the β and β-like genes are clustered on chromosome 11. The various hemoglobin are expressed at various times during development via globin switching. For example, HbA₂ (α₂δ₂) and HbF (α₂γ₂) are expressed primarily during gestation.

There are four α genes and two β genes in a diploid genome. β mutations are more likely than α mutations to cause disease because each β gene accounts for half of all β chains (versus only 1/4 for each α gene). β mutations do not affect fetuses since the β-like &gamma chain is fetally expressed; however, α mutations can severely impact both fetal and postnatal life.

Locus Control Region

The locus control region (LCR) is a ∼20 kb region that is ∼6 kb upstream from the εG_γA_γψβδβ cluster of β and β-like genes. It contains five DNase1 hypersensitive sites, necessary to open the chromatin and allow transcription factors to activate the regulatory regions. Without the LCR, none of &epsilon, γ, ψ, δ nor β chains are expressed. The genes are expressed in the same order through development as their location on the chromosome via an unclear mechanism.

β locus

β globin locus has cis-acting elemtns in promoter and immediatel flanking regions for temporal control of β-like globin genes, but the LCR location 8 to 22kb upstream in the e-globin gene is what is needed for high level of β cluster gene expression. LCR contains at least four DNase I hypersensitive sites, provided an open chromatin domain for easy access of trnscription factos to regulatory elements in the cluster.

α locus

LCR of the alpha-globin cluster is HS-40, a DNase I hypersensitive site located 40 kb upstream of the z globin gene, is necessary for high level expression of genes in the alpha globin cluster.

Natural selection has favored people who like fatty foods. This is because fatty foods contain lipids, which have the most calories per liter. Therefore, the person who eats the most lipids is the least likely to starve. Evolution has shaped our food preferences. There are 3 important macromolecules:

When caloric intake is reduced as much as 50%, the effects have been shown to be:

• Longer lifespan.
• Lower incidence of cancer.
• Slower onset of age-related dementia.
• No ovulation (reduced reproductive capacity).

The lack of ovulation is typical when diet is restricted (as in anorexic women). Although the positive effects of caloric restriction are negligible in social animals such as humans, the effects in rodents, insects, and microbes are remarkable. The lifespan of a praying mantis is in some cases doubled when the praying mantis is calorically restricted.

There are two well-respected explanations:

• Since organisms devote most of their energy to reproduction, when the reproductive organs shut off then more energy is available for other functions. This has a positive effect on health.
• When less food is processed, less free radicals are digested and generated. Since free radicals damage mitochondria and reduce efficiency of cells, having less free radicals means that cells will function better and longer. As a result, the being as a whole will be healthier.

Sources: Dr. Farabee

What Is the Endocrine System?

Endocrine glands secrete hormones (chemical messengers) into the blood. Hormones act on target cells, which must have appropriate receptors to bind the hormone and bring about a physiological response. The endocrine system is composed of endocrine glands located throughout the body, and generally regulates activities that require duration, rather than speed.

What Is A Hormone?

Hormones are long-range chemical messengers secreted into the bloodstream by endocrine (ductless) glands in response to an appropriate signal, and carried in the blood to other sites in the body where they exert their effects on target cells some distance from their site of release. Hormones generally produce their effects by altering intracellular protein activity.

Hormones are classified into three categories based on their structure:

• Peptides: Comprise most hormones, including those secreted by the hypothalamus, anterior and posterior pituitary, pancreas and parathyroid.
• Amines: Derived from the amino acid, tyrosine, and include the hormones secreted by the thyroid gland, and adrenal medulla. Adrenomedullary hormones are called catecholamines.
• Steroids: Neutral lipids derived from cholesterol; include hormones secreted by the adrenal cortex, ovaries and testes. Steroid and thyroid hormones are lipid soluble (lipophilic).

For a more in-depth analysis of what is a hormone, click here.

Several important hormones are insulin, growth hormone, antidiuretic hormone, prolactin, gonadotropins and endorphins.

Hormone-Secreting Glands

The primary hormone-secreting glands are:

• Pituitary Gland (anterior pituatiary secrets GH which i a protein stimulating protein synthesis and growth) (depression at bottom of skull just over back of roof of mouth)
• Hypothalamus

The other hormone-secreting glands are:

• Sex Organs (ovaries: endrogens & progesterones; testes: androgens) (gonads)
• Adrenal Glands (adrenal medulla secrets epinephrine, norepinephrine, modified amino acids stimualte flight-or-flight…increase heart, redistriubute blood to muscles, raise blood surgar.) (Adrenal cortex secrets glucocorticoids (cortisol) sterioids targeting muscles, immune system, and other tissues to mediate response to stress, reduce metabolism of glucose, increase metabolism of proeins and fats, reduce inflammation and immune responses.) (adrenal gland sits above each kindey.)
• Thyroid Gland (secretes calcitonin, which is a peptide acting on bones to stimulate bone formaiton and lower blood calcium.) neck (parathyroid raises blood calcium)
• Pancreas (insulin)
• Pineal Gland (secretes melatonin a modified amino acid to hypothalamaus for slep et al)

For the entire chapter on hormone-secreting glands, click here.

Other Chemical messengers

Interferons are proteins released when a cell has been attacked by a virus. They cause neighboring cells to produce antiviral proteins. Once activated, these proteins destroy the virus.

Prostaglandins are fatty acids that behave in many ways like hormones. They are produced by most cells in the body and act on neighboring cells.

Pheromones are chemical signals that travel between organisms, rather than between cells within an organism. In the animal world, pheromones are heavily used to mark territory, signal prospective mates and to communicate. The presence of a pheromone as a human sex attractant has not been established conclusively.

Potential Defects of the Endocrine System

• Overproduction of a hormone
• Underproduction of a hormone
• Nonfunctional receptors that cause target cells to become insensitive to hormones

Keratinocytes produce keratin, which toughens and waterproofs the skin.

1. define “carcinoma”.
2. define “malignant”.
3. define “metastatic”.
4. briefly describe basal cell carcinoma.
5. briefly describe squamous cell carcinoma.
6. briefly describe malignant melanoma.
7. identify the ABCDs of examining skin cancer lesions.
a. A – asymmetric shape.
b. B – border that is irregular or diffuse.
c. C – color that is pearly or multicolored.
d. D – diameter that is greater than 5mm.

Surface Patterns

Congenital lines are fingerprints (friction ridges). They were formed by the pull of eleastic fibers within dermis, and are present on palms and soles. The four basic combinations are: arch, whorl, loop, and combination.

Acquired lines include deep flexion creases on palms and flexion lines that are seen on surface of joints (such as knuckles).

Skin Coloration

There are 3 important pigments which give the skin color and protection:

• Melanin is a brown-black pigment produce by melanocutes of stratum basale. It protects against the ultraviolet (UV) rays of the sun.
• Carotene is a yellowish pigment found in certain plants, such as carrots. It accumulates in the cells of the stratum corneum and fatty parts of the dermis. It is not the cause of the yellow-tan skin of Asian people; melanin variants are.
• Hemoglobin in oxygenated blood flowing through the dermis gives the skin pinkish tones.

The skin and its accessory structures (glands, nails, and hair) constitute the integumentary system. The skin is an organ because it conssits of several kinds of tissues that are structurally arranged to function together. It covers approximately 3000 sq. in, making it the largest organ. It is of variable thickness, averaging 1.5 mm. It is thickest on area of high friction, such as the soles and palms, where it is 6 mm thick. It is thinnest on the eyelids, external genitalia, and tympanic membrane, where it is .5 mm thick. It variable texture as well: it can be rough and callous, such as on the elbows and knees; it can be soft and sensitive, such as on the genitalia.

It has three main layers, with the outermost being the epidermis, the middle one being the dermis, and the innermost one being the hypodermis aka subcutaneous layer.

The major cells and structures of skin are:

Click for more information on integumentary surface structures and integumentary cells.

Below are the three levels of burn severity, as well as some important information.

• 1^st Degree Burn: rednes, pain and no tissue damage (sunburn).
• 2^nd Degree Burn: blistering, pain and upper epidermal damage.
• 3^rd Degree Burn: no pain (no remaining nerves), charred epidermis, exposed and damaged dermis; is life-threatening if over large body surface.

What Is the Lymphatic System?

Blood in the heart is highly pressurized, but most of that pressure is lost as blood flows through arteries and then arterioles. At the capillary level, most remaining pressure is lost as blood leaks out into tissues. This leaked fluid is unable to go against the pressure gradient back into the bloodstream, so instead diffuses into lymph capillaries of the lymphoid system. Once fluid has been absorbed into the lymphatic system it is called lymph. Lymph has almost the same composition as blood.

The lymphatic system’s primary function is to keep the blood circulatory system a closed system that allows transfer only out of vessels. By definition, all fluids outside of cells and not in the bloodstream are by definition lymph. Once lymph diffuses into lymph capillaries from capillary tissues, it coalesces into lymph vessels of increasing size. These vessels form into ducts which, at the neck, eventually dump lymph back into the bloodstream.

The lymphatic system’s secondary function is to completely drain the body of fluid, and screen this lymph for invaders. The lymphatic system has high concentrations of white blood cells to mount a response, including lymphocytes, macrophages and dendritic cells — but no granulocytes.

The lymphatic system has no central pump; however, its vessels have one-way valves through which lymph flows. This flow is driven by skeletal muscles milk the lymph along as the body moves. Lymph passes through progressively larger vessels, eventually arriving in the right lymphatic duct (for fluid from the right upper body) or the thoracic duct (for the rest of the body). These ducts drain into the circulatory system in the neck, at the right and left subclavian veins.

Lymph vessels are present in gastrointestinal lining, absorbing fats and dumping them into the thoracic duct. The thoracic duct then drains these fats directly into the blood circulatory system. After passing through the stomach, food enters the small intestine. Chyle is the lipid-rich lymph drawn from the small intestine. The liver processes all nutrients present in the circulatory system, including the chyle that has been dumped into the bloodstream.

If you are learning immunology, then please read about lymph nodes before continuing.

Primary Lymphoid Organs

Bone marrow and the thymus are the primary lymphatic organs (aka central lymphoid tissues). Lymphocytes are produced by stem cells in the bone marrow and then migrate to either the thymus or bone marrow where they mature. T-lymphocytes undergo maturation in the thymus, and B-lymphocytes undergo maturation in the bone marrow. After maturation, both B- and T-lymphocytes circulate in the lymph and accumulate in secondary lymphoid organs, where they await recognition of antigens.

Secondary Lymphoid Organs

The spleen, lymph nodes, and accessory lymphoid tissue are the secondary lymphoid organs (aka peripheral lymphoid tissues). These organs contain a scaffolding that support circulating B- and T-lymphocytes and other immune cells like macrophages and dendritic cells. When micro-organisms invade the body or the body encounters other antigens (such as pollen), the antigens are transported from the tissue to the lymph. The lymph is carried in the lymph vessels to regional lymph nodes. In the lymph nodes, the macrophages and dendritic cells phagocytose the antigens, process them, and present the antigens to lymphocytes, which can then start producing antibodies or serve as memory cells to recognize the antigens again in the future.

The spleen contains lymphocytes that filter the blood stream rather than the lymphatics. Thus, the spleen has importance in fighting infections that have invaded the blood.

Mucosa-associated lymphoid tissue is specialised lymphoid tissue associated with the mucosa of a number of organs.

Lymph enters a lymph node via an afferent vessel, and leaves via efferent vessels. Inside the lymph node, lymph percolates through various layers of tissue. The lymph then continues on its path into the blood circulatory system.

BK channels (aka Slo channels) are tuned via alternative splicing of α subunit exons, thereby controlling regulatory properties, conductance and voltage sensitivity of the channel. BK Channels are present in muscle tissue and in the cochlea

The nervous system has three levels of organization:

An axon often has to navigate great distance to reach its target cell (ie, another neuron or muscle fiber) and establish the synaptic connection. This process is axonal pathfinding. The axon does not navigate its natural pathway due to any single cue, but via combinations of signals. This redundancy makes axonal pathfinding extremely complex. Axonal pathfinding is extremely specific: a particular axon always contacts the same (or at least very similar) set of neurons or muscles.

Neurons have an intrinsic polarity that is always the same for a specific type of neuron. At one end of this polarity, a localized increase in cell membrane activity occurs (with ruffles, aka lamellipodium often visible) and fine filopodia of the cell cytoplasm extend and withdraw. The structure of filopodia is maintained by microfilaments, while axonal strucure is maintained by microtubules. Eventually, a filopodium forms a growth cone, an actively motile region at the far end.

The growth cone travels based on cues from a substrate called the extracellular matrix (ECM). The ECM contains laminin, collagen and fibronectin (the first being the most important) that adhere to cadherins and integrins in the growth cone membrane. Also, the ECM contains unique molecules (ie, nerve growth factor and retinoic acid) that guide the growth cone, sometimes across a gradient and other times along a narrow path. These unique molecules are deposited: by tissues over which the axons grow (ie, epithelia, somites and blood vessels); by cells at crucial migratory points; and even by the target tissue itself.

Once the growth cone reaches its specific target (ie, muscle fibers or another neuron) it must stop growing and establish a synaptic connection. The high specificity of axonal pathfinding is determined by any of three ways:

Netrin

Commisural neurons are interneurons in the (usually dorsal) spinal cord that extend their axons across the midline. Commisural projects project ventrally toward the floor plate, and then cross the midline ventral to the floorplate of the spinal cord. Recombination experiments have shown that the floor plate secretes netrin, an attractive signal critical for commisural axons to migrate to the floor plate and cross the midline. In netrin^-/- mutants, commisural axons fail to grow to the floor plate.

Ehprin

Ephrins are membrane-bound ligands that bind to membrane-bound ephrin-receptors called ephs. When an ephrin and an eph bind, a signal is generated in both cells — this means the signal is bi-directional. Ephins are repulsive signals in axon migration, with ephrin/eph signaling responsible for setting the retino-tectal topographic map. In a topographic map, the spatial organization of neurons in one region (retina) is replicated in a connected region (tectum). The retina and tectum contain inverse gradients of ephs and ephrins; axons extend from the retina to the tectum until reaching a signaling threshold (inversely proportionate to their starting point) that inhibits further navigation. Thus, axons from a retinal region with low levels eph will target a tectal region with high levels of eph. In the figure below, axons from a given retinal quadrant will target the tectal quadrant of matching color.

All in all, ephrin/eph signaling is critical for:

1. motor neurons extending only through the anterior of a somite;
2. setting the retino-tectal topographic map;
3. inhibiting mixing — rhombomeres, compartments in the hindbrain across which cells do not mix, express ephrins and ephs.

Neurons cluster together to form ganglia. Usually, one ganglia is larger and more central than others. This ganglia is called the brain. In vertebrates, most cells of the nervous system are found in the brain and spinal cord. This is where most information processing, storage and retrieval occurs.

Neurons vary considerably in size and shape, but have 3 principal components: a cell body and two types of cytoplasmic extensions (an axon and dendrites).

All but one type of neuroglia (glial cells) are derived from same ectoderm that produces neurons. Most organs are from the mesoderm. There are six categories of neuroglia:

• Neurolemmocytes (Schwann cells) form myelin layers around axons in the PNS.
• Oligodendrocytes form myelin layers around axons in the CNS.
• Microglia are derived from mesoderm and remove foreign and degenerated material in the CNS.
• Astrocytes help regulate passage of molecules from blood to brain.
• Ependymal cells line brain ventricles and central canal of spinal cord
• Ganglionic gliocytes support neuron cell bodies within ganglia off the PNS.

The Sodium/Potassium Pump puts Na⁺ outside the cell and K⁺ inside the cell.

• 3Na⁺ mols inside bind to receptor
• This stimualtes phosphorylation of receptor by ATP.
• This alters receptor shape, shape change dumps Na⁺ onto inside.
• Open receptors bind 2K⁺ ions outside.
• K⁺ binding triggers phosphate release.
• This restores original conformation.
• K⁺ released inside, NA⁺ sites become available.
• Net: 1 ATP lost; 3 Na⁺ outside; 2 K⁺ inside.

Voltage is the tendency for electrically charged particles such as electrons or ions to move between two points. The principle of voltage is the foundation for action potentials. The action potential is a wave of depolarization of a neuron’s plasma membrane. This depolarization requires a resting membrane potential of about -70 millivolts, with the interior of the cell negatively charged. Two proteins are required to establish the resting membrane potential:

Na⁺ ATPase and potassium leak channels are the two proteins required to establish the resting membrane potential. These proteins are integral membrane proteins in the plasma membrane. The Na⁺K⁺ ATPase hydrolizes one ATP molecule to pumps three sodium ions out of the cell and two potassium ions into the cell. The Na⁺K⁺ ATPase uses ATP to drive transport against their gradient. This transport of ions against their gradient, while hydrolizing ATP, is an example of primary active transport. The result is a gradient with plentiful sodium outside the cell and plentiful potassium inside the cell.

Potassium leak channels allow potassium ions, but no other ions, to flow down their gradient. Since Na⁺K⁺ ATPase causes an overabundance of potassium ions inside the cell, the potassium ions will flow through the potassium leak channels back outside the cell. Since potassium ions are positive, they will leave the interior of the cell with a net negative charge. The potential across the plasma membrane is about -70mV, the resting membrane potential.

All cells have a resting membrane potential; neurons and muscle tissues are unique in using the resting membrane potential to generate action potentials. The flow of potassium out of the cell makes the interior of the cell more negatively charged. If the potassium leak channels were blocked, the interior of the cell would have a less negative (more positive) charge. If sodium ions were allowed to flow down their concentration gradient, they would flow into the cell and the interior of the cell would have a less negative (more positive) charge.

The resting membrane potential establishes a negative charge along the interior of the axons along with the rest of the neuronal interior. An action potential is a disturbance in this membrane potential, a localized depolarization of the plasma membrane that travels in a wave-like manner along an axon. Depolarization is a change in the membrane potential from the resting membrane potential of approximately -70 mV to a less negative or even positive potential. The change in membrane potential during an action potential is caused by movement of ions into and out of the neuron through ion channels. The action potential is not strictly an electrical impulse, like electrons moving in a copper telephone wire, but an electrochemical impulse.

A key protein in the propagation of action potentials are the voltage-gated soidum channels located in the plasma membrane of the axon. In response to a change in the membrane potential, these ion channels open to allow sodium ions to flow down a gradient into the cell and depolarize that section of membrane. Opening the voltage-gated sodium channels would allow sodium ions to flow into the cell (down the concentration gradient) and make the interior of the cell less negatively, or even positively, charged. These channels are opened by depolarization of the membrane from the resting potential of -70 mV to a threshold potential of approximately -50 mV. Once this threshold is reached, the channels are opened fully; below this threshold, though, they do not allow the pssage of any ions through the channel. When channels open, sodium flows into the cell (down the concentration gradient) and depolarizes that section of the membrane to about +35 mV before inativating. Some of the sodium ions flow down the interior of the axon, slightly depolarizing the neighboring sectino of the membrane. Whn the depolarization reaches -50 mV i the next section of membrane, those voltage-gated sodium channels open as well. This opening of more voltage-gated sodium channels passes the depolarization down the axon. Since action potentials are continually renewed at each point in the axon as they travel, action potentials can’t run out of energy before reaching a synapse. Once they begin, they will not stop until that synapse is reahed.

After depolarization, repolarization returns the membrane potential to normal.

na+ channels open to gwenerate an action potential
upstream na+ channels inactivate making membrane refractory…K_ channels open and axon repolarizes
action potential jumps quickly to new node and contnues from node to node

Steps in an Action Potential:

1. At rest the outside of the membrane is more positive than the inside.
2. Sodium moves inside the cell causing an action potential.
3. The positive sodium ion influx makes the inside of the membrane more positive than the outside
4. Potassium ions flow out of the cell, restoring the resting potential net charges.
5. Sodium ions are pumped out of the cell and potassium ions are pumped into the cell, restoring the original distribution of ions.

Gametogenesis is the development of germ cells into gametes. Gametes are large nonmotile oocytes in females, and small motile sperm in males. Gametogenesis occurs in the gonads: ovaries in females and testes in males. The two main differences between oogenesis and spermatogenesis: prophase arrest; and unequal division.

II. The Skeletal System (axial & appendicular divisions):
A. Locate and identify the major bones of the body (see lab list).
1. we will cover these in lab – you are responsible for them in lecture also.
B. The skull.
1. locate & identify cranial and facial bones.
2. locate and identify the four major cranial sutures.
3. define and describe the following:
a. fontanelles.
b. microcephaly.
c. paranasal sinuses.
d. deviated nasal septum.
e. cleft palate.
C. The spinal column.
1. locate and identify the spinal bones:
a. cervical vertebrae (7).
b. thoracic vertebrae (12).
c. lumbar vertebrae (5).
d. sacrum (1).
e. coccyx (1).
2. define and describe the following terms:
a. scoliosis.
b. lordosis.
c. kyphosis.
d. spina bifida.
3. know male/female pelvic distinctions:

Intremembraneous ossification involves the replacement of sheet-like connective tissue membranes with bony tissue. Bones formed in this manner are called intramembraneous bones. They include certain flat bones of the skull and some of the irregular bones. The future bones are first formed as connective tissue membranes. Osteoblasts migrate to the membranes and deposit bony matrix around themselves. When the osteoblasts are surrounded by the matrix they are called osteocytes.

Endochondral ossification involves the replacement of hyaline cartilage with bony tissue. In this process, the future bones are first formed as hyaline cartilage models. During the third month after conception, the perichondrium that surrounds the hyaline cartilage “models” become infiltrated with blood vessels and osteoblasts and change into a periosteum. The osteoblasts form a collar of compact bone around the diaphysis. At the same time, the cartilage in the center of the diaphysis begins to disintegrate. Osteoblasts penetrate

I. Bone Basics:
A. Identify the major functions of the skeletal system.
1. physical protection & support.
2. calcium storage.
3. blood cell production.

Below are three increasingly-magnified photos of a histology slide featuring human bone. Notice the structure of the bone.

B. Define the following anatomical terms:

1. diaphysis.
2. epiphysis.
3. epiphyseal (growth) plate.
4. articular cartilage.
5. periosteum.
6. compact bone tissue & distribution.
7. spongy bone tissue & distribution.
C. Identify the functions the cells found in bone.
1. osteoblast (bone-builder).
2. osteoclast (bone-dissolver).
3. osteocyte (bone-maintainer).
D. Identify and describe the composition and function of bone matrix.
1. calcium phosphate minerals.
2. collagen fibers.
E. Identify and describe the location, composition and function of bone marrow.
1. red bone marrow.
2. yellow bone marrow.
F. Define the following bone tissue terms:

a. lamellae.
b. osteon.
c. central (Haversian) canal.
d. canaliculi.

There are three kinds of bone growth: endochondral ossification (for long bone growth); intramembranous ossification (for flat, irregular bone growth); and remodeling (role of osteoblasts and osteoclasts).

Describe the structural/functional classifications of joints: fibrous/immovable joints; cartilaginous/slightly movable joints; synovial/freely movable joints.
Describe the basic structure of synovial joints including:
1. synovial membrane and capsule.
2. synovial fluid.
3. articular cartilage.
4. bursae.

Distinguish between the functions of tendons and ligaments.

Shoulder joint:
1. identify the bones and structures comprising the shoulder joint.
2. identify the “rotator cuff” muscles.
a. supraspinatus.
b. infraspinatus.
c. subscapularis.
d. teres minor.

Knee Joint:
1. identify the bones and structures comprising the knee joint.
2. identify the major groups of knee ligaments.
a. collaterals (medial & lateral).
b. cruciates (anterior & posterior).
c. patellar.

Bone & Joint Disorders:
1. Briefly describe the following disorders (structures involved, manifestations, etc.).
a. bursitis.
b. rheumatoid arthritis.
c. osteoarthritis.
d. osteoporosis.

Below are brief descriptions of the major integumentary cells:

Cochlear Hair Cells are tuned to respond to different sound frequencies. These cells are arrayed in a tonotopic gradient, with low frequency responders at the apical end of the cochlea and high frequency responders at the basal end. Birds and reptiles uses alternative splicing of BK Channels as one facet of tuning these hair cells to transduce different sound frequencies. Isolation of cochlear cell mRNA has revealed that each cell expresses a different subset of BK Channel mRNA.

Sources: Dr. Walker

Requires joining of two haploid cells (gametes) to form a diploid individual. Gametes are produced by gametogenesis, a process involving meiotic cell divisions. Two meiotic events contribute to genetic diversity: crossing over between homologous xsms and independent assortment of xsms. Sexual reproduction itself contributes much genetic diversity, because the two parents have tremendous xsmal disparity. There are three fundamental steps:

• Gametogenesis (making gametes)
• Mating (getting together gametes)
• Fertilization (making gametes fuse)

Gray crescent is where sperm-binding sits are located. When the sperm enter the cytoplasm rotates toward site of sperm entry. This reveals band of pigmented cytoplasm on egg opposite sperm entry site. This is called the grey crescent.

Rearrangements of egg cytoplam set stage for determination. β-catenin is a crucial transcription factor from materanl mRNA found through cytoplasm. Also protein kinase GSK-3, which phospohorylates and inactivates β-catenin. In the vegal cortex of egg is GSK-3 inhibitor. This inhibitor is oved along microtubules to the gray crescent where it keeps β-catenin from being ddegraded.

Cleavage: rapid cell divisions leading to bundle of cells is called cleavage. IThe cytoplasm is not homogeneous so distriubition of nutreints plays a role in determinants of cells of early embryo. No cell growth and little expression just replication. This balls forms a central fluid-filled cavity blastocoel (morula is just the ball of cells). The embryo is now a blastulate with individual cells called blastomeres.

The amount of yolk influences cleavage. IN embryos with little or n yolk then cleavage furrow formation is simple. More yolk means more resistance to cleavage furro formation. The blastodisc results from incomplete furrow formation. Otherwise you have complete cleavage.

Orientation of mitotic spindles determines planes of cleavage and therefore arrangement of daughter cells.

Gastrulation: producing the body plan

• Fertilization
• The sea urchin is one of the several model organisms that has been used to decipher the basic cellular and molecular biology of animal fertilization.
• More is known about fertilization in sea urchins than is known about fertilization in most vertebrates.
• In animals in general, fertilization is the direct interaction and fusion of two germinal cells (one “egg” and one spermatozoan), resulting in the initiation of cleavage, gastrulation and the species-specific developmental program that characterizes each organism.
• In sea urchins, a discrete series of steps characterizes fertilization (Vacquier, 1998).
• Attraction of spermatozoa by fully mature ova
• Peptides dissolve from the jelly coat and stimulate sperm respiration, motility and chemoattraction in a species-specific manner.
• Sperm follow a decapeptide gradient in sea water towards the region of higher concentration at jelly coat of recently spawned fully mature ova.
• These peptides have been recovered from egg-conditioned medium.
• In S. purpuratus and Hemicentrotus pulcherrimus, the peptide is entitled speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) and in Arbacia punctulata the peptide is called resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-gly-Gly-Gly-Arg-Leu).
• Species specificity depends on the COOH end of the peptide and deletion of the Val or Val-Gly residues results in loss of respiration-stimulating activity.
• A 767 amino acid protein that serves as a voltage sensitive channel in the plasma membrane of the spermatozoan has been isolated from the testis of S. purpuratus.
• Such a channel might become activated by speract-induced hyperpolarization and lead to flagellar beating.
• Activation & Acrosomal Reaction of Spermatozoa
• Activation of the many spermatozoa which triggers the acrosomal reaction results from direct their contact with a highly sulfated fucose sulfate polymer in the jelly coat of the fully mature ovum.
• This interaction causes adherence of many spermatozoa to the jelly coat and opening of incurrent Ca2+ channels in their cell membranes that are similar to human polycistin-L.
• The acrosomal reaction results in fusion of the acrosomal vesicle membrane with the spermatozoan plasma membrane and permits the release or secretion of the contents of the acrosomal vesicle.
• Hydrolytic enzymes from the acrosomal vesicle begin to digest constituents of the jelly coat.
• Additionally, excurrent proton pumps in sperm membrane are also opened at this time and their activity leads to alkalinization of the cytoplasm in the head of the spermatozoan.
• Alkaline cytoplasm promotes the loss of profilactin blocking protein from ends of actin monomers.
• Explosive polymerization of actin generates microfilaments that extend a membrane covered acrosomal process from the bottom of the vacant acrosomal vesicle.
• The acrosomal process projects through the remains of the jelly coat towards the vitelline membrane of the egg.
• As this occurs, bindin (not a glycoprotein or a transmembrane protein) becomes associated in an unknown manner with the tip of the acrosomal process.
• Sea urchin bindins are not related to any other proteins, but they do contain a central domain of 60 amino acids that has been conserved for over 150 MY.
• Also released from the acrosomal vesicle at this time are syntaxin and VAMP which become involved in secretion of the contents of the granule granules of the fully mature ovum following fertilization.
• Binding of the membrane of spermatozoa with the vitelline membranes of fully mature ova:
Binding receptors on the vitelline membrane recognize and attach to bindin protein on the tip of the acrosomal process.
• Sea urchin egg receptor for bindin is a complex molecule that is still very controversial.
• The putative receptor is a single protein that has several domains and is unlike any known class of receptors.
• On its carboxyl terminus it has a short cytoplasmic domain, followed by a single membrane spanning domain.
• Extracellular domains on the amino termins include a potential vitelline membrane spanning domain followed by a domain that is similar to cytoplasmic heat shock 70 proteins in the vertebrates.
• Since the function of heat shock proteins is to bind to and fold other proteins, perhaps this HS70 domain can bind bindin.
• Subsequent to these analyses, other researchers have disputed the validity of this interpretation, even suggesting that the protein identified as the bindin receptor is actually a soluble, cytoplasmic HS110 protein.
• Resolution of this issue will await further sequence data.
• Fusion of the cell membrane of the spermatozoan with that of the fully mature ovum:
• While thousands of spermatozoa can potentially achieve this level of interaction with the fully mature ovum, the vitelline membrane is finally breached by the acrosomal process of a single spermatozoan.
• The membrane of this spermatozoan fuses with that of the fully mature ovum.
• Why only one spermatozoan is capable of this act, when many are marsheled to accomplish the same task is one of the unanswered questions of sea urchin biology.
• Activation of the cytoplasm, the cortical reaction of the fully mature ovum and assembly of the fertilization envelope:
After fusion, the metabolism of the egg changes radically during activation.
• The membrane of the fully mature ovum is depolarized radially away from point of fusion.
• Gamete membrane fusion elicits a wave of Ca2+ release from intercellular stores that initiates at the point of fusion and causes exocytosis of some 15,000 cortical granules.
• Included in these granules is
• 1) hyalin which forms a layer immediately surrounding the egg,
• 2) a colloid that raises the fertilization membrane by imbibing H20,
• 3) a serine protease (CGSP1) that destroys receptors for sperm on the vitelline membrane,
• 4) a protein termed vitelline delaminase that may cleave the connection between the vitelline membrane and the oolemma,
• 5) a structural protein that in the presence of H202 is polymerized onto the inner surface of the old vitelline membrane, now called the fertilization membrane
• 5) ovoperoxidase, a heme-dependent peroxidase that functions to block polyspermy by interacting with the structural protein mentioned above in the presence of H2O2 to form the new fertilization membrane
• The increase in respiration within the cytoplasm of the newly fertilized egg produces H202 which serves as the oxidant for the catalysis of the structural proteins to the inside of the old vitelline membrane by dityrosine crosslinkages.
• The consideralbe oxidative damage that could result from the presence of H202 evolved in this process is countered by an intracellular amino acid called ovothiol.
• Ovothiol is oxidized to the disulfide thus consuming H202.
• There results a highly protective shield, the fertilization membrane, that protects the fertilized fully mature ovum or zygote.
• Pronuclear Fusion
• Within the cytoplasm of the newly formed zygote, the centriole near the female pronucleus generates an array of microtubules.
• Internalization of components of the sperm is accomplished using a myosin molecular motor and the microtubules of the acrosomal process.
• The haploid male pronucleus and the centriole and some cytoplasm from the spermatozoan are drawn into the cytoplasm of the egg.
• The nucleus of the spermatozoan swells and becomes the male pronucleus and its centriole generates an array of microtubules.
• Female and male pronuclei fuse following their migration towards each along their respective microtubular arrays.
• Either the female pronucleus migrates to the male or the male pronucleus migrates to the female and resulting fusion of the membranes of these pronuclei produces the diploid zygote nucleus.
• The chromosomes from these nuclei have already undergone pre-meiotic S-phase during which they replicated their DNA.
• Mitotic cleavage divisions follows and generate the blastula.
• Cleavage</li.
  • Cleavage is a mechanism for cloning the zygote genome generated at fertilization following male and female pronuclear fusion.
  • Usually in edible sea urchins, cleavage is oligolecithal, indicating that a limited amount of yolk (= nutritional molecules) is present in the cytoplasm mostly of the vegetal pole of the egg.
  • Many informational molecules, like the protooncogene c-myc are present in the cytoplasm in stored form, as untranslated mRNA with short polyA tails.
  • Intracellular signalling pathways that result in the first cleavage division are just now coming into focus and they bear a striking similarity to the initiation of the cell cycle in somatic cells.
  • There is a mechanism for the release of calcium. Account for a Ca2+ increase and alkalinization of the cytoplasm. Phospholipase Cgamma is involved in fertilization and cleavage. Calcium transient requires production of inositol triphosphate.
  • Yet not clear how MAP kinase pathway is involved. For example, c-myc is already present and this common denominator can upregulate expression of G1 cyclins that promote the cleavage cell cycle.
  • Maybe donÕt need the cytoplasmic phosphorylation cascade that accompanies induction of mitosis in somatic cells, since myc protein is already there. Otherwise this is one of the major functions of the MAP-kinase based phosphorylation cascade.
• Gastrulation
• Gastrulation is when many organisms begin to express the new embryonic genome formed during fertilization.
• Up until this point, maternal informational molecules were used laid down during oogenesis.
• Many urchins die at gastrulation as lethal combinations of genes produce either non-functional or defective proteins.
• MYP is digested by cathepsin B in such early embryos. MYP was produced during the pregametogenesis and NP renewal stage and was transferred intact to primary oocytes during oogenesis.

• Males produce the smaller gamete.
• Females produce the larger gamete.
• Hermaphrodites produce both male and female gametes.

Male Reproductive System

Testes: tightly coiled semineferous tubules (sperm produced here). epididymis outside testes where sperm mature (where sperm get mobile). The epididymis is connected to the urethra via the vas deferens.

Acrosome, DNA, mitochondria, tail. Leydig cells between semineferous tubules produce testosterone.

Making sperm. Spermatogonium.

In the presence of testosterone and at slightly lower than body temperature, haploid motile sperm are continuously produced during a man’s life.

Sperm wars: lots of cuckoldry results in more sperm production. Gorillas are monogamous. Chimps are polygomous. Humans are in the middle.
______ ______
/ \ / \fallopian tubes
| \/ |
\O /\ O/ovaries
|_|cervix, uterus
| |
| |
| |vagina

An ovarian cycle
1) low est…pituitary releases fsh
2) follicles develop, produce est
3) at maturity follicle produces progesterone
4) Hi est…pit releases surge of lh/fsh
5) surge causes ovulation
6) follicle secretes less estrogen, more progesterone
7) Uterine lining thickens.
8) If fertilized: HCG from blastocyst keeps it producing estrogen/progesterone. If unfertilized: corpis luteum degenerates, estrogen and progesterone decline (menstruation)
Repeat

A follicle is stimulated to develop into a large fertile egg by coordinated secretions of estrogen, FSH, and LH. Uterus prep is coordinated by progesterone.

How do birth control pills work? low levels of estrogen, but not so low to cause fsh production. progestin produces slight thickening of uterine lining and at neck of cervix to block sperm. low enough level of progestin to make implantation possible. What is the difference between ovariectomizing a pet and just tying the fallopian tubes? Why might it benefit members of a species to conceal ovulation?

Concealed…human. Obvious…most mammals.

—

Fetal sexual development…undifferentiated gonads. If testes determining factor (TDF) is present then gonads becomes testes. Otherwise, they become ovaries. TDF is on the Y-chromosome. Gonads make steroid hormones. If ovaries: estrogen. If testes: testosterone. Undifferentiated ducts start connecting. If testosterone present and converted to DHT become penis/testes. If DHT present, become vagina. What happens if an XY individual has no androgen receptors?

Embryos develop female internal/external organs unless a y-chromosome stimulates testes development leading to testosterone production which stimulates male sex organ development.

—

Fertilization
1) contact…sperm find jelly coat of egg.
2) acrosomal rxn…release hydrolytic enzymes, escavate hole in jelly coat.
3) acrosomal process grows to bind to receptors on vitelline layer.
3) Fusion of plasma membranes

Fusion triggers the fast block to polyspermy: after 1-3 seconds, ion channels open, Na+ rushes in, depolarized membranes keep other sperm out.
Cortical rxn
granules in egg fuse with plasma membrane, discharge enzymes breaking bond between viteline envelope and plasma membrane. H2O flows in, fert membrane forms, slow block to polyspermy.

**At fertilization, a sperm penetrates the egg membrane and egg blocks additional sperm entry electrically and physically.

Early cleavage…even cleavage or uneven, or incomplete

Right after fertilization comes cleavage, many rapid cell divisions without growth. In early division the fertilized egg udnergoes cleavage divisions and blastula formation even without the presence of a nucleus. Genes in zygote are not necessary.

Cleavage continues…blastula forms about 128 to 10,000 cell hollow ball….gastrulation where rearrangement to produce body plans, 3 distinct layers of tissue form…

Endoderm: lining of digestive tract and respiratory system
Mesoderm: skeleton, muscles, bone
Ectoderm: skin, nervous system

Gray crescent, infolding. Blastocoel is hollow inside. Dorsal lip of blastopore. Next is archenteron (gut, the inside of infolding) and ectoderm is outside and endoderm lines achenteron and mesoderm is around it.

Gastrulation result is same inall taxa: embryo with gut and 2 or 3 germ layers.

Autodidact

Oral contraceptives contain synthetic steroids that inhibit release of GnRH and then of FSH and LH, so no egg is released. However, the estrogen and progesterone in the pill supports the uterine cycle; suspension of the pill each month permits menstruation.

Two new hypothalamic peptides work in opposition to control :
Gonadotropin-inhibiting hormone (GnIH) inhibits and kisspeptin stimulates GnRH secretion.

A differentiated part of an organism, such as an eye, wing, or leaf, that performs a specific function. It is composed of a tissue or tissues which function together.

Pituitary Gland consists of a stalk linking the pituitary to the hypothalamus, which controls release of pituitary hormones. The pituitary gland has two lobes: the anterior and posterior lobes.

The anterior pituitary is a glandular structure under contorl of the hypothalamus. Together, the pituitary gland and hypothalamus control many endocrine functions. They secrete many hormones, some of which are crucial for the female menstrual cycle, preganncy, birth, and lactation. These important hormones include follicle-stimulating hormone (FSH), which stimulates development and maturation of a follicle in one of a woman’s ovaries, and leutinizing hormone (LH), which causes the bursting of that follicle (= ovulation) and the formation of a corpus luteum from the remains of the follicle.

The posterior pituitary stores and releases hormones into the blood. Antidiuretic hormone (ADH) and oxytocin are produced in the hypothalamus and transported by axons to the posterior pituitary where they are dumped into the blood. ADH controls water balance in the body and blood pressure. Oxytocin is a small peptide hormone that stimulates uterine contractions during childbirth.

The hypothalamus produces releasing hormone TRH (thyrotropin releasing hormone) that causes the anterior pituitary to release TSH (thyroid stimulating hormone) that cause the thyroid gland to release thyroid hormones. Thyroid hormones (thyroxine and triiodothyroxonine) regulate carbohydrate metabolism by cells, and early in life, are involved in growth. Low circulating levels increase TRH and TSH output; high levels reduce their output. Goiter.

Posterior Pituitary Gland

Cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus send axons via the pituitary stalk to terminals in the posterior pituitary that release two hormones into the bloodstream. Vasopressin, a.k.a. antidiuretic hormone (ADH), acts on the kidney to inhibit formation of urine, to conserve water and increase blood pressure.

Oxytocin stimulates contraction of the uterus during childbirth, triggers the milk letdown reflex during nursing, and may be the “love” hormone, released by terminals outside the hypothalamus.

Although suckling alone causes oxytocin release at first, the mother may become conditioned to release oxytocin upon hearing the baby’s cry. Thus, higher faculties can control hypothalamic and thus hormonal output.

Anterior Pituitary Gland (tropic hormones)

Hypothalamic cells produce specific releasing hormones and inhibiting hormones, which they secrete from axon terminals in the median eminence into a portal system of blood vessels to flood the anterior pituitary, causing the latter cells to release their specific tropic hormones. Tropic hormones are pituitary hormones that affect other endocrine glands.

The anterior pituitary releases six tropic hormones:

Hypothalamus releases gonadotropin Releasing hormone (GnRH), causing pituitary to release LH (stiumalting ovulaiton) The hypothalamus contains neurons that control releases from the anterior pituitary. Seven hypothalamic hormones are released into a portal system connecting the hypothalamus and pituitary, and cause targets in the pituitary to release eight hormones. Hypothalamus receptors monitor blood levels of thyroid hormones. Low blood levels of Thyroid-stimulating hormone (TSH) cause the release of TSH-releasing hormone from the hypothalamus, which in turn causes the release of TSH from the anterior pituitary. TSH travels to the thyroid where it promotes production of thyroid hormones, which in turn regulate metabolic rates and body temperatures.

Sex Organs, which not only produce gametes but also secrete sex hormones. Sex hormone secretion is controlled by the pituitary gland hormones such as FSH and LH. While both sexes make some of each of the hormones, typically male testes secrete primarily androgens including testosterone. Female ovaries make estrogen and progesterone in varying amounts depending on where in her cycle a woman is. In a pregnant woman, the baby’s placenta also secretes hormones to maintain the pregnancy.

Adrenal Glands are located one above each kidney. The adrenal gland is divided into an inner medula and an outer cortex. The medulla synthesizes 2 hormones, epinephrine (adrenaline) and norepinephrine. When the sympathetic nervous system stimulates the cortex causes hormones related to fight-or-flight to get secreted into the blood. The adrenal cortex produces several steroid hormones in 3 classes: mineralocorticoids (maintain electrolyte balance), glucocorticoids (long-term, slow response to stress by raising blood glucose levels by breaking down fats and proteins, and also suppresss immune system and inhibit inflammatory response), and corticosteroids such as cortisone (which are anti-inflammatory hormones suppressing secretion, and suppress immune system.

In response to ACTH from the pituitary gland, the adrenal cortex makes adrenocorticoids. These include

1. Glucocorticoids, like cortisol, increase blood glucose, cause protein breakdown, and are anti-inflammatory.
2. Mineralocorticoids, specifically aldosterone, which acts on kidneys to retain sodium and conserve water.
3. Sex steroids, specifically androstenedione.

The adrenal medulla secretes epinephrine (adrenaline) and norepinephrine in response to sympathetic activity from the hypothalamus.

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The pancreas contains exocrine cells and endocrine cell clusters. Exocrine cells secrete digestive enzymes into the small intestines.

Endocrine cell clusters (aka pancreatic islets or islets of Langerhans) secrete insulin and glucagon. Insulin and glucagon regulate blood glucose levels. After a meal, when blood glucose levels rise, insulin is released so that cells can uptake the elevated glucose levels. Liver and skeletal muscles form glycogen, a carbohydrate. As glucose levels fall, insulin production is inhibited. Glucagon causes breakdown of glycogen into glycose, which is in turn released into the blood to maintain homeostatic glucose levels. Glucagon production is stimulated by low blood glucose levels, and inhibited when they rise.

In this sense, the pancreas serves as a ductless gland by regulating blood glucose levels:

• When blood glucose levels rise, insulin is released so that cells uptake the glucose and it is removed from the bloodstream. Also, the liver and skeletal muscles store glucose as a carbohydrate named glycogen.
• When blood glucose levels drop, glucagon is released so that the glycogen in liver and skeletal muscles is released as glycose. This maintains homeostatic blood glucose levels.

When blood glucose levels are not properly regulated, diabetes results. For example, if not enough insulin is produced (or the liver does not properly respond) then blood sugar can rise out of control and the result is diabetes mellitus. Diabetes causes impairment in functioning of eyes, circulation, CNS & PNS, and kidneys; it is the 2^nd leading cause of death. The two major types of diabetes are shown below:

• Type I Diabetes involves inadequate levels of insulin secretion, usually from a genetic cause. This results in blood glucose levels to rise, possibly out of control.
• Type II diabetes develops in adults form both genetic and environmental causes. Loss of response of insulin targets rather than lack of insulin causes this.

Relevant Articles

1. Insulin
2. Hormones

The pineal Gland secretes melatonin and is one of the brain’s only unitary structures. The pineal gland is located near the center of the human brain, and is stimulated by nerves from the eyes. In some other animals, the pineal gland is close to the surface of the skin and is directly stimulated by light. The pineal gland secretes melatonin at night (dark) and, as a result, secretes more melatonin in winter when the nights are longer. Melatonin promotes sleep and decreases activity of the gonads. In addition, melatonin affects thyroid and adrenal cortex functions and (in some animals) skin pigmentation.

Relevant Articles

1. Melatonin
2. Hormones

Although not a gland, it is important to note that the stomach lining secretes gastrin, a pepide, into the stomach. Gastrin promotes digestion by stimulating release of digestive juices and stimulates stomach movements that mix food and digestive fluids.

The stomach lining is part of the exocrine system, which operates via ducts like sweat and the digestive enzyme described above.

The average adult contains 2-3 liters of bone marrow, a primary lymphoid organ located in the core of long bones. Bone marrow is composed of myeloid tissue (tissue capable of hematopoiesis) and has three major functions: production and support of stem cells; B cell maturation; and antibody production.

Bone marrow has a definite architecture, with environments containing unique factors to guide differentiation of each cell type. The myeloid tissue promotes differentiation into different cell types based on signals from outside the barrow marrow. Bone marrow also contains memory B cells, similar to lymph node germinal centers.

The dermis is thicker and deeper than the epidermis. Elastic and collageous fibers are arranged in definite patterns to produce lines of tension and provide skin tone. There are many more elastic fibers in the dermis of a young person than an old one. The extensive network of blood vessels in the dermis provides nourishment to the living portion of the epidermis. The dermis also contains many sweat glands, oil-secreting glands, nerve endings, and hair follicles.

Innervation and Vascular Supply

• Nerve supply: specialized integumentary effectors consist of smooth muscles or glands within the dermis that respond to motor impulses from central nervous system. Several types of sensory receptors respond to various tactile, pressure, temperature, tickle or pain stimuli.
• Vascular supply: blood vessels within dermis supply nutrients to mitotically active stratum basale, and to structures of the dermis. Dermal blood vessels also play an important role in temperature regulation.

Layers of the Dermis

The dermis is composed of two layers. The outermost dermal layer is listed first:

• Stratum papillarosum: in contact with epidermis, and accounts for 1/5 of entire dermis. Papillae form the base for friction ridges on fingers and toes.
• Stratum reticularosum: fibers within this layer are more dense and organized to forma tough, flexible meshwork. It is very distensible, but can be torn when stretched too far. Linea albicans, which appear as temporary white streaks, form when a torn dermis repairs itself.

The presence of hair is a distinguishing feature of mammals. Men and women have the same density of hair, but testosterone makes the hair more apparent on men. The primary functions of hair are protection and attraction.

Each hair consists of a diagonally positioned shaft, hair and bulb. The shaft is the visible, but dead, portion of the hair projecting above the surface of the skin. The bulb is the enlarged base of the root within the hair follicle. Each hair develops from stratum basale cells within the bulb of the hair, where nutrients are received from dermal blood vessels. As the cells divide, they are pushed away from the nutrient supply toward the surface, and cellular death and keratinization occur.

In a healthy person, hair grows at the rate of approximatel 1 mm every 3 days. As the hair becomes longer, however, ti enters a resting period where there is minimal growth. The life span of a hair varies from 3 to 4 months for an eyelash to 3 to 4 years for a scalp hair. Each hair lost is replaced by a new hair that grows from the base of the follicle and pushes the old hair out. Between 10 and 100 pairs are lost daily.

3 layers can be observed in hair that is cut in cross section. The inner medula is composed of loosely arranged cells separated by numerous air cells. The thick cortex surrounding the medula consists of hardened, tightly packed cells. A cuticle covers the cortex and forms the toughened outer layerof the hair. Cells of the cuticle have serrated edges that give it a scaly appearance under the microscope.

Hair color is determine by type and amount of pigment produced in stratum basale at base of hair follicle. Varying amounts of melanin produce from blond to brunette to black. More melanin, darker. Trichosiderin, a pigment with an iron base, produces red hair. Gray or white hair is lack of pgiment and air spaces within layers of shaft of hair. Texture of hair is based on cross-sectional shape: straight hour round, wavy hair oval, kinky hair flat.

Sebaceous glands and arrectores pilorum are attached to hair folicle. Arrectores pilorum muscles involuntary, responded to thermal or pyschological stiumli. When contract, hair pulld into more vertical position to make goose bumps. Three kinds of hair:

Lanugo: fine, silky fetal hair appears during last trimester of development seen only on premature infants
Vellus: shrort, fine hair replacing lanugo. Abundant in children and women just barely extended from the hair follicules.
Terminal hair: coarse, pigment (except in elderly people) and sometimes curly. It includes scalp, pubic, eyelash hair.
Angora hair is terminal hair growing continually as in scalps and faces of mature males.
Definitive hair grows to a certian lengths and stops, including eyelashes.

Introduction & Layers

The epidermis is the superficial protective layer of the skin. It is derived from the ectoderm, and is composed of stratified squamous epithelium that varies in thickness from .007 to .12 mm. All but the deepest layers are composed of dead cells. Areas exposed to high friction have 5 layers; areas not exposed to high friction have 4 layers. Beginning with the innermost layer, the epidermis is composed of the following layers:

• Stratum basale consists of a single layer of cells in contact with the dermis. Four types of cells constitute this layer:
  • Keratinocytes are specialized cells producing keratin. As keratinocytes are pushed away from the vascular nutrient and oxygen supply of the dermis, they undergo keratinization: their nuclei degenerate and their cellular content becomes dominated by keratin.
  • Melanocytes are specilized epithelial cells which produce melanin.
  • Tactile cells are sparse relative to keratinocytes and melanocytes, and are involved in tactile (touch) reception.
  • Nonpigmented granular dendrocytes are scattered throughout the stratum basale. They are protective macrophagic cells which ingest bacteria and other foreign debris.
• Stratum spinosum is oftentimes grouped with the stratum basale. This complex is called the stratum germinativum
• Stratum granulosum contains 3 or 4 flattened alyers of cells. These cells contain granules filled with keratohyalin, a chemical precursor of keratin.
• Stratum lucidum appears clear because the nuclei, organelles and cell membranes are no longer visible. It exists only in the lips, soles, and palms.
• Stratum corneum is composed of 25 to 30 layers of flattened, scalelike, dead cells. It has been cornified, which is a process brought on by keratinization, which means that it has been dried and flattened.

Below are brief descriptions of the major integumentary structures:

Hormones generally produce their effects by altering intracellular protein activity.

Hormones bind with specific target cell receptors; starting a chain of events in the target cell which produce effects characteristic of that hormone. Based on the location of their receptors, hormones can be classified into 2 groups:

1. Hydrophillic peptides and catecholamines, being poorly soluble in lipid, are unable to cross the lipid bilayer and bind to specific plasma membrane receptors.
2. Lipophillic steroids and thyroid hormones cross the lipid bilayer and bind to specific intracellular receptors.

Water-soluble (hydrophillic) hormones dissolve into the cytoplasm; lipophilic hormones are bound to membrane-bound proteins.

Hormone responses can differ based on the target cell
A hormone acting on its target cell receptor, produces a characteristic response in the target cell, which is different for different hormones, and differs between different target cells responding to the same hormone;
eg. an adrenal medullary catecholamine, epinephrine, can produce the following effects:
contraction of vascular smooth muscle
relaxation of respiratory airway smooth muscle
breakdown of liver glycogen

Hormones ultimately affect their target cells by altering activity of proteins within the cell, generally by one of the following mechanisms:

1. most hydrophilic hormones binding to cell surface receptors, produce a second messenger molecule within the target cell (hormone is the “first” messenger)
2. a few hydrophilic hormones following binding to cell surface receptors, alter cell permeability by opening or closing particular ion channels
3. lipophilic hormones through binding to intracellular receptors, activate specific genes (through transcriptional regulation within the nucleus), leading to the formation of new intracellular proteins which produce a characteristic physiological effect

Cytoplasmic hormone receptor

Types of cell-surface receptors
Ligand-gated ion channels – eg. acetylcholine receptor
G-protein-linked receptors – guanyl nucleotide binding proteins (G proteins) act as molecular switches; active when GTP is bound, inactive with GDP due to action of intrinsic GTPase
Enzyme-linked receptors – eg. insulin receptor

Each hormone has a specific shape that binds to receptors on target cells. These binding sites are called hormone receptors. Many hormones come in antagonistic pairs, where each has opposite effects on the target organs. Hormonal regulation relies heavily on feedback loops to maintain balance and homeostasis. Most animals with well-developed nervous and circulatory systems have an endocrine system. The endocrine systems of crustaceans, arthropods, and vertebrates are very similar due to convergent evolution. The vertebrate endocrine system consists of glands (pituitary, thyroid, adrenal), and diffuse cell groups scattered in epithelial tissues. More than fifty different hormones are secreted. Endocrine glands arise during development for all three embryologic tissue layers (endoderm, mesoderm, ectoderm). The type of endocrine product is determined by which tissue layer a gland originated in. Glands of ectodermal and endodermal origin produce peptide and amine hormones; mesodermal-origin glands secrete hormones based on lipids. There are two classes of hormones: steroids (derived from cholesterol) and peptides (derived from amino acids). They are secreted into body fluids and reach many cells, but only target cells respond. The endocrine system is similar, using chemicals to communicate. These are known as hormones. A hormone is a specific messenger molecle synthesized and secreted by a group of espcialized cells called an endocrine gland. These are ducltless, meaning their secretions (hormones) are released directly into the bloodstram and travel elsewhere in the body to target organs upon which they act.Note that this is in contrast to our digestive glands, which have ducts for ereleasing digestive enzymes.The nervous system coordinates rapid and precise responses to stimuli using action potentials. The endocrine system maintains homeostasis and long-term control using chemical signals. The endocrine system works in parallel with the nervous system to control growth and maturation along with homeostasis.

Hypothalamus: Gonadotropin-releasing hormone (GRH)
Ant. Pituitary: Luteinizing hormone & follicle-stimulating hormone
Testes: Testosterone Ovaries: Estradiol and Progesterone

Leutinizing hormone (LH) causes the bursting of the follicle in a woman’s ovaries, and also facilitates the formation of a corpeus luteum from the remains of the follicle.

Polypeptides are short chains of amino acids; most hormones are peptides. They are secreted by the pituitary, parathyroid, heart, stomach, liver, and kidneys.

Peptide hormones are synthesized as precursor molecules and processed by the endoplasmic reticulum and Golgi where they are stored in secretory granules. When needed, the granules are dumped into the bloodstream. Different hormones can often be made from the same precursor molecule by cleaving it with a different enzyme.

Pituitary Hormones

• Oxytocin
• Vasopressin (antidiuretic hormone, ADH)
• Melanocyte-stimulating hormones (MSH)
• Corticotropin (adrenocorticotropin, ACTH)
• Lipotropin (LPH)
• Thyrotropin (thyroid-stimulating hormone,TSH)
• Growth hormone (GH, or somatotropin)
• Prolactin (PRL)
• Luteinizing hormone (LH)
• Human chorionic gonadotropin (hCG)
• Follicle-stimulating hormone (FSH)

Hypothalamic Hormones

• Corticotropin-releasing factor (CRF or CRH)
• Gonadotropin-releasing factor (GnRF or GnRH)
• Prolactin-releasing factor (PRF
• Prolactin-release inhibiting factor (PIF)
• Growth hormone-releasing factor (GRF)
• Somatostatin
• Thyrotropin-releasing factor (TRH or TRF)

Thyroid Hormones

• Calcitonin
• Calcitonin gene-related peptide (CGRP)
• Parathyroid hormone (PTH)

Digestive Hormones

• Gastrin
• Secretin
• Cholecystokinin (CCK)
• Motilin
• Vasoactive intestinal peptide (VIP)
• Gastrin inhibitory peptide (GIP)
• Somatostain

Pancreatic Hormones

• Insulin
• Glucagon
• Pancreatic polypeptide
• Somatostatin
• Peptide Hormones

Steroids are lipids derived from cholesterol. Testosterone is the male sex hormone. Estradiol, similar in structure to testosterone, is responsible for many female sex characteristics. Steroid hormones are secreted by the gonads, adrenal cortex, and placenta.

Steroid hormones are derived from cholesterol by a biochemical reaction series. Defects along this series often lead to hormonal imbalances with serious consequences. Once synthesized, steroid hormones pass into the bloodstream; they are not stored by cells, and the rate of synthesis controls them.

Amines are derived from the amino acid tyrosine and are secreted from the thyroid and the adrenal medulla. Solubility of the various hormone classes varies.

Amine hormones (notably epinephrine) are stored as granules in the cytoplasm until needed.

Melatonin promotes sleep and decreases activity of the gonads. In addition, melatonin affects thyroid and adrenal cortex functions and (in some animals) skin pigmentation. Because melatonin production is affected by the amount of light to which a person is exposed, this is tied to circadian rhythm (having an activity cycle of about 24 hours), annual cycles, and biological clock functions. SAD or seasonal affective disorder (syndrome) is a disorder in which too much melatonin is produced, especially during the long nights of winter, causing profound depression, oversleeping, weight gain, tiredness, and sadness. Treatment consists of exposure to bright lights for several hours each day to inhibit melatonin production. It has also been found that melatonin levels drop 75% suddenly just before puberty, suggesting the involvement of melatonin in the regulation of the onset of puberty. Studies have been done on blind girls (with a form of blindness in which no impulses can travel down the optic nerve and reach the brain and pineal gland), which showed that these girls tended to have higher levels of melatonin for a longer time, resulting in a delay in the onset of puberty. While some older people, who don’t make very much melatonin, thus don’t sleep well, might benefit from a melatonin supplement, I’m skeptical of the recent melatonin craze in this country. When so many people apparently are suffering from SAD, I question the wisdom of purposly ingesting more melatonin, especially since the pineal gland is one of the least-studied, least-understood of the endocrine glands.

Insulin is a peptide hormone secreted by the pancreas and results in the lowering of blood sugar levels. It acts on liver, fat, muscle and other tissues to stimulate uptake of glucose. Uptaken glucose is either metabolised or converted to glycogen and fat. After a meal, when blood glucose levels rise, insulin is released so that cells can uptake the elevated glucose levels.

Glucagon is a peptide hormone that acts upon the liver to stimulate breakdown of glycogen and raise blood sugar levels.

Relevant Articles

1. Pancreas
2. Hormones

Pheromones are also communication chemicals used to send signals to other emmebers of same species. Queen bees, ants, and naked mole rats exert control of their respective colonies via pheromones. THey are commonly used to attract mates, for….Pheromones are widely studied in insects and are the basis for some kinds of Japanese beetle and gypsy moth traps. While pheromones have not been so widely studied in humans, some interesting studies have been done in recent years on pheromonal control of menstrual cycles in women. It has been found that pheromones in male sweat and/or sweat from another “dominant” female will both influence/regulate the cycles of women when smeared on their upper lip, just below the nose. Also, there is evidence that continued reception of a given man’s pheromone(s) by a woman in the weeks just after ovulation/fertilization can significantly increase the chances of successful implantation of the new baby in her uterus. Pheromones are also used for things like territorial markers (urine) and alarm signals.

Growth hormone (GH) is a peptide anterior pituitary hormone essential for growth. GH-releasing hormone stimulates release of GH. GH-inhibiting hormone suppresses the release of GH. The hypothalamus maintains homeostatic levels of GH. Cells under the action of GH increase in size (hypertrophy) and number (hyperplasia). GH also causes increase in bone length and thickness by deposition of cartilage at the ends of bones. During adolescence, sex hormones cause replacement of cartilage by bone, halting further bone growth even though GH is still present. Too little or two much GH can cause dwarfism or gigantism, respectively.

One non-sex hormone secreted by the posterior pituitary is antidiuretic hormone or ADH. This hormone helps prevent excess water excretion by the kidneys. Ethanol inhibits the release of ADH and can, thus, cause excessive water loss. That’s also part of the reason why a group of college students who go out for pizza and a pitcher of beer need to make frequent trips to the restrooms. Diuretics are chemicals which interfere with the production of or action of ADH so the kidneys secrete more water. Thus diuretics are often prescribed for people with high blood pressure, in an attempt to decrease blood volume.

Another group of non-sex hormones that many people have heard of is the endorphins, which belong to the category of chemicals known as opiates and serve to deaden our pain receptors. Endorphins, which are chemically related to morphine, are produced in response to pain. The natural response to rub an injured area, such as a pinched finger, helps to release endorphins in that area. People who exercise a lot and push their bodies “until it hurts” thereby stimulate the production of endorphins. It is thought that some people who constantly over-exercise and push themselves too much may actually be addicted to their own endorphins which that severe exercise regime releases.
the thyroid gland.

Gonadotropins and secreted by the anterior pituitary. Gonadotropins influence the gonads. Gonadotropins (which include follicle-stimulating hormone, FSH, and luteinizing hormone, LH) affect the gonads by stimulating gamete formation and production of sex hormones.

Prolactin are also secreted by the anterior pituitary. Prolactin is secreted near the end of pregnancy and prepares the breasts for milk production.