Endocrine System Lecture Notes

The neurohypophysis has supportive tissues known as pituicytes.
- Pituicytes support and nourish neuronal cells.

Oxytocin is a nonapeptide hormone, meaning it consists of nine amino acids.
- It is involved in a reflex arc from the nipples and uterus.
- Originates from SON (supraoptic nucleus) and PUN (paraventricular nucleus).
- The cleaved portion of oxytocin is produced in association with neurophysin (a carrier protein).
- Functions:
- Stimulates mammary gland and uterine smooth muscle contractions.
- Works through GPCR-PLC (G Protein-Coupled Receptor - Phosphoinositide-specific phospholipase C) pathway, ultimately increasing intracellular calcium ions (Ca²⁺).
- Similar structure to AVP (arginine vasopressin), differing primarily at position 3 (instead of Lysine, it has Isoleucine).
- Proteolysis of its prohormone occurs in vesicles before release.

Neural stimuli that trigger oxytocin release include:
- Signals from the breast and spinal cord.
- Relayed to the midbrain then to SON/PUN via excitatory acetylcholine (Ach) or inhibitory norepinephrine (NE).
- Neural stimulus leads to depolarization which causes exocytosis of oxytocin.

Prostaglandins relay and amplify stretch signals locally from mechanoreceptors in the breast that respond to suckling signals, causing contraction of myoepithelial cells within the mammary gland.

The mammary gland is lined with capillaries and alveoli, filled with milk.
- Functional structures include:
- Myoepithelial cells that can contract to help eject milk from the alveoli.
- During pregnancy, milk secretion is kept low due to high levels of progesterone.
- Estrogen increases levels of oxytocin, promoting muscle contractions for milk ejection.

Besides its primary role in lactation, oxytocin also:
- Induces vascular smooth muscle contraction.
- Influences umbilical arteries and veins during fetal development.
- Plays a role in maternal behavior, mating behaviors in females, and social behaviors.
- Reduces anxiety levels.

AVP, also known as Antidiuretic Hormone (ADH), is highly homologous to oxytocin and is secreted when plasma becomes hypertonic causing osmoregulation.
- Synthesized in magnocellular neurons within the posterior pituitary, associated with neurophysin.
- Major functions include:
- Renal nephron reabsorption of water.
- Constriction of peripheral blood vessels to increase blood pressure.

Pressor activity:
- Vasoconstrictive action that increases blood pressure when body water content decreases.
Antidiuretic activity:
- Aids in water reabsorption when body is dehydrated.

The genes for oxytocin and AVP are located next to each other and are very similar due to recent gene duplication, which has led to neofunctionalization—resulting in their separate functions.

Neural stimuli from the midbrain and PVN (paraventricular nucleus) activate AVP release:
- Ach or NE leads to depolarization and vesicle release from the posterior pituitary.
Osmoreceptors located in the anterolateral hypothalamus measure blood osmolality (concentration of solutes in the blood).

With low blood osmolality (dilute blood):
- Osmoreceptors become inactive and swell, inhibiting AVP secretion.
With high blood osmolality (concentrated blood):
- Osmoreceptors become stimulated and shrink, leading to increased AVP secretion.
Sodium chloride (NaCl) is very effective as an osmotic stimulus, while glucose is not.

Baroreceptors located in the carotid sinus and aortic arch measure blood pressure and respond as follows:
- Significant blood pressure decreases lead to reduced baroreceptor activity, resulting in AVP release.
- When blood pressure is normal, baroreceptors are active and inhibit AVP by releasing norepinephrine.

Both osmoreceptors and baroreceptors can signal a single AVP neuron:
1. Peripheral blood pressure declines (hypotonic):
- Blood becomes hypertonic due to decreased water.
- Osmoreceptors shrink and fire Action potentials (AP) sending neurosecretory signals to release AVP from the posterior pituitary.
1. Water reabsorption occurs in kidneys, leading to increased blood pressure.

Vasoconstriction in smooth muscle which aids in increasing blood pressure.
In the kidneys, it acts by:
- V2 Receptor Activation:
  - Through activation of adenylate cyclase (AC), raises cAMP levels leading to an antidiuretic response.
- V1 Receptor Activation:
  - Stimulates vasoconstriction and platelet aggregation.

AVP stimulates water channel localization in cell membranes through upregulation of aquaporins (AQPs):
- AQP2 located in the collecting ducts are vital for water reabsorption.
- AQP1 predominantly in the proximal tubule is responsible for resorbing most glomerular filtrate.

AVP increases the permeability of the collecting duct membranes by promoting the insertion of AQP2 channels:
1. Increased presence of AQP2 channels on the apical membrane allows water to move from urine into cells.
2. Water then exits through AQP3 and AQP4 on the basolateral side back into the blood.
3. Phosphorylation of AQP2 channels is mediated by protein kinase A (PKA), which is activated by cAMP from the V2 receptor pathway:
  - PKA induces AQP2 vesicle translocation to the membrane.

Under conditions of dehydration, the following occurs:
1. Water loss leads to increased osmolality or low blood pressure.
2. Osmoreceptors detect shrinkage and fire AP, leading to AVP release after inhibiting baroreceptors from releasing NE.
3. Post pituitary releases AVP, prompting kidneys to absorb water, which subsequently increases blood pressure and decreases osmolality.

Diabetes Insipidus: results from loss of AVP function, leading to an inability to concentrate urine, causing:
- High urine volume.
- Decreased solute concentration and increased thirst.
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): characterized by excessive release of AVP without regard to osmolality levels, requiring AVP antagonists and reduced water intake for management.