Antidiuretic hormone

Neurohypophysis

Posterior pituitary - stores and releases hormones made in the hypothalamus

Nuclei in the hypothalamus

Paraventricular - makes mostly oxytocin

Supraoptic - makes mostly ADH

Neurosecretory cells from these nuclei extend axons down into posterior pituitary

ADH characteristics

Antidiuretic Hormone - Vasopressin

Controls water retention and vasoconstriction

Peptide hormone (9 amino acids → nonapeptide)

Synthesis and storage of ADH

Synthesized in supraoptic and paraventricular nuclei as prehormone

Stored and released from the neurohypophysis

Transported down axons of hypothalamic neurons via Neurophysin 2, carrier protein that binds and stabilises ADH (protection and folding)

V1 receptors - vascular smooth muscles → vasoconstriction, V2 - kidney collecting ducts → promote water reabsorption

Triggers for ADH release

Increased plasma osmolarity → detected by hypothalamic osmoreceptors

Decreased blood volume → detected by mechanoreceptors in right atrium

Decreased blood pressure → sensed by baroreceptors in aorta and carotid sinus

Others - stressors (pain, nausea, emotion), age, alcohol (inhibits), drugs

ADH effect on kidneys

ADH binds to V2 receptors on basolateral membrane of collecting duct cells

Activation of G protein → stimulates adenyl cyclase → converts ATP to cAMP

cAMP activates PKA (protein kinase A)

PKA phosphorylates proteins which moves Apuaporin-2 water channels to apical membrane

Water from urine now pass into cell and then blood, making urine more concentrated and the body retains water

ADH effect on blood vessels

ADH binds to V1 receptors on surface of vascular smooth muscle cells

This activates G protein (Gq) inside cell → this activates Phospholipase C

PLC breaks down a lipid molecule on membrane called PIP2 into IP3 and DAG

IP3 moves into cytoplasm and releases calcium, DAG stays in membrane and helps activate Protein Kinase C which aids in contraction

Calcium levels rise inside muscke cell, calcium binds to calmodulin → activates Myosin Light Chain Kinase → helps actin and myosin filaments slide

Smooth muscle in vessel wall contracts → blood vessel narrow → blood pressure rises

Physiological roles of ADH

Water balance - retains water during dehydration, concentrates urine

Blood pressure reg - vasoconstriction via V1 receptors

Thirst stimulation - acts on hypothalamic thirst center

Renal effect - impact on collecting tubules to control urine volume and concentration

Hydration states

Dehydration → more ADH → more water absorbed → concentrated urine

Overhydration → less ADH → less water absorbed → diluted urine

Diabetes insipidus

Dysfunction in the reabsorption of water

Can be caused by a defect in ADH production and secretion or a defect in the kidneys response to ADH

Can cause polyuria (excessive urination), polydipsia (excessive thirst)

Can be treated by the administration of exogenous ADH