Posterior Pituitary Hormones

Mechanism of Bromocriptine

Dopamine agonist —> stops cAMP and decreases transcription of prolactin

Use of bromocriptine

• Used for hyperprolactinemia

• Acromegaly

• Small GH producing tumors

How does prolactin modulate GnRH and Estrogen

Prolactin can negatively affect GnRH, which will in turn decrease FSH and LH production, which can decrease estrogen production

Does vasopressin induce water retention or water elimination?

Goal of vasopressin is to increase BV:

Therefore, we would increase water retention via

• Controls aquaporin tubes via GPCR cAMP

• ADH binds to its receptor in the collecting ducts. When the blood delivers vasopressin -> triggers cAMP - moves tubes to the membrane and water is reabsorbed into the body 

A 7-year-old boy underwent successful chemotherapy and cranial radiation for Treatment of acute lymphocytic leukemia. One month after the completion of therapy, the patient presented with excessive thirst and urination plus hypernatremia. Laboratory testing revealed pituitary diabetes insipidus. To correct these problems, this patient is likely to be treated with which of the following?

A. Corticotropin

B. Desmopresin

C. hCG

D. Menotropins

E. Thyrotropin

HYPERnatremia = high salt

We want to reabsorb water yes? How do we do that? Vasopressin analogue IE increase water reabsorption via desmopressin

Vasopressin antagonists

Conviaptan and Tovaptan

What 2 hormones are released by the posterior pituitary

Oxytocin and Vasopressin

Oxytocin receptors activate:

GPCR, triggers IP3 and phospholipase C —> increase influx of calcium —> stimulates muscle contraction

Oxytocin leads to

Milk stimulation, uterine contraction

Prostaglandin and leukotriene release

Induce labor

Oxytocin antagonist

Atisoban

Nifendipine is a CCB used for this purpose but is controversial

Vasopressin MOA?

• ADH binds to the receptor and activates adenylyl cyclase → cyclic AMP → protein kinase a → movement of aquaporins to the apical membrane (the side with the pee). This allows for more water to move out of the collecting duct back into the blood for reabsorption. (Diuretics block this and make us pee to lower BP)

Role of prolactin?

• Principle hormone for lactation, stimulated by circulating estrogen, progestin, corticosteroids, and insulin

Mediators of prolactin

• Prolactin does not have a direct hypothalamic releasing hormone, but it can be regulated by other hormones 

• TRH can increase prolactin

• Estrogen can increase prolactin

• Dopamine can block prolactin

Excess prolactin leads to:

• Fertility problems (alters feedback mechanism of estrogen and can alter ovulation, as estrogen excess can lead to GnRH inhibition) 

• Loss of libido

Causes of prolactin secretion:

• PRL stimulation in primary hypothyroidism or adrenal insufficiency 

• Increase PRL production can occur via pituitary tumors or PCOS 

• Pregnancy

• Hepatic insufficiency or renal failure (reduced clearing of prolactin)

Effect of opiates and neuroleptics on dopamine:

These typically inhibit dopamine release. If dopamine typically negatively affects prolactin release, then removing the inhibitor allows for less downregulation of dopamine and thus increase dopamine levels.  (hyperprolactinemia is a side effect of antipsychotics)

Effect of bromocriptine on prolactin?

Bromocriptine is a dopamine agonist

Dopamine activates gai to block cAMP production. This decreases the transcription of prolactin and suppresses prolactin release 

This reduces prolactin expression 

Therapeutic use of bromocriptine 

• Dopamine receptor agonists reduce PRL

• Can shrink pituitary prolactin secreting tumors

Examples of dopamine agonists:

Bromocriptine, cabergoline (ergot derivative) 

Quinagolide, pramipexole, ropinirole (nonergot) ← antiparkinson treatment, give them dopamine and anticholinergics

What neurohormone is released in the anterior pituitary but acts directly on its target organs?

Prolactin

How is oxytocin activated?

Activates GPCR, which activates Phospholipase C →  IP3 pathway → , which results in release of calcium, which leads to muscle contraction. This releases milk and stimulates uterine contraction and stimulates prostaglandin and leukotriene release

Therapeutic use of oxytocin

Release milk, induce labor 

Can be used to control uterine hemorrhage

What is a physiological trigger that will release vasopressin

Release is triggered by rising tonicity (high salt in the blood will trigger the reabsorption of water) or falling BP 

Released by the kidney to increase water retention

ADH activates a GPCR adh receptor. This enhances cAMP to activate PKA, which triggers the movement of aquaporins (water channels) to move to the apical membrane. This induces water reabsorption to increase BP

Modified vasopressin analogue:

• Desmopressin, long lasting analog and more selective to V2 

Desmopressin therapeutic use:

• Can be used to treat mild hemophilia A

• Diabetes Insipidus (inability to control water levels in the blood due to pituitary insufficiency)

Use for vasopressin antagonists

• Used in hyponatremia, antagonize the binding of add to the receptor and block the reabsorption of water. This increases excretion and increases the tonicity of the blood by removing the water volume to concentrate the blood with more salt