2C Posterior Pituitary review

Which hormones are released from the posterior pituitary?

Arginine vasopressin (AVP)

Oxytocin (OT)

What type of hormones are released from the posterior pituitary?

Both AVP and OT are 9 AA peptides

How is the regulation of posterior pituitary hormones different from anterior pituitary hormones?

Not associated with target endocrine organ; not a part of an axis

How are posterior pituitary hormones synthesized?

Transcription→translation→post-translational modification

What is the first structure produced in posterior pituitary hormones synthesis? Where is it produced?

Preprohormone; transcripted in the nucleus, translated in ribosomes

What is the second structure produced in posterior pituitary hormones synthesis? Where is it produced?

Prohormone; post-translational modification in the ER)

What is the final structure produced in posterior pituitary hormones synthesis? Where is it produced?

Active hormone; post-translational modification in secretory vesicles

Outline the cellular mechanisms needed for release of AVP and/or OT.

CNS neurons synapse with dendrites/cell bodies of SON/PVN neurons (induce EPSPs or IPSPs) →

Adequate depolarization allows membrane potential to reach threshold, inducing AP. →

Voltage-gated Ca channels open on axon terminals and stimulate secretory vesicles exocytosis.

What happens to AVP and/or OT after release?

Enters ECF of posterior pituitary, diffuses into fenestrated capillaries & enters circulation.

What stimulated SON/PVN neurons leading to OT release?

Afferent signaling initiated by cervical distention, or tactile stimuli from nursing or milking.

Where is the OT receptor expressed, what is the receptor type & what is the result of receptor activation?

OT receptor (OXTR); Gq-linked GPCR on myometrial cells. Promotes smooth muscle contraction by increasing cytoplasmic [Ca].

Or, myoepithelial cell contraction, stimulating milk letdown.

Outline the positive feedback pathway associated with OT.

Myometrial contractions put pressure on fetus, stimulating further cervical distention & thus OT release.

Where is the AVP receptor expressed & what is the receptor type?

Vasopressin-2 receptor (V2); Gs-linked GPCR on base lateral membrane of renal tubular epithelial cells

What is the result of V2 receptor activation?

Increased squalor in-2 (AQP-2) synthesis; allows increased H2O entry to cell.

increased V2 receptor activation leads to what systematic effects?

Increased H20 reabsorption from renal tubules

Increased H2O returned to blood & decreased H20 excretion via urine

Increased BV, decreased osmolarity

What are Osmoreceptors & how do they regulate AVP neurons in the SON/PVN?

Neurons in the hypothalamus that detect small changes in osmolarity. Synapse on AVP-producing neurons and signal via EPSPs.

How do changes in ECF osmolarity alter AVP release?

Increased osmolarity (dehydration, cells shrink) = increased AP frequency, increased AVP production

What are volume receptors & how do they regulate AVP neurons in the SON/PVN?

Cardiovascular volume receptors (mechanoreceptors) in atrial wall. Stimulate inhibitory neurons via EPSP’s.

How do changes in ECF volume alter AVP release?

Increased BV (overhydration, cells shrink), increased AP frequency → increased inhibition of AVP producing neurons → decreased AVP production

Where is the AVP receptor expressed & what is the receptor type?

Vasopressin-1 receptors (V1); Gq-linked GPCR on vascular smooth muscle

What is the result of receptor activation?

Activation → increased cytoplasmic [Ca] → increased smooth muscle contraction

What clinical signs would you expect with diabetes insipidus?

Increased urination and thirst

Dilute urine

Rapid dehydration when water is restricted

how might you diagnose diabetes insipidus?

Measure plasma [AVP]

Water deprivation test

Exogenous administration of AVP