Posterior pituitary hormones

Prolactin

199 aa peptide hormone, secreted by lactotrophs in the anterior pituitar

DA receptor agonist - inhibits anterior pituitary hormone release

Posterior pituitary hormones

oxytocin

vasopressin (ADH)

prolactin: control

hypothalamic control is dominant inhibition by dopamine

estrogen stimulates lactotroph cells in pituitary to release the hormone

prolactin (PRL) in pregnancy and lactation

levels increase in pregnancy, promotes breast development while pregnant

during pregnancy, high levels of estrogen/progesterone inhibit lactation. Fall of these hormones postpartum triggers lactation

PRL stimulates lactation in postpartum period

Level is maintained postpartum by nipple stimulation of breast feeding

Hyperprolactinemia

usually caused by a PRL-secreting pituitary adenoma (prolactinoma)

more common in women

chronically high PRL suppresses hypothalamic-gonadal-pituitary axis

Symptoms: galactorrhea, oligomenorrhea or amenorrhea, infertility and loss of libido in men

PRL receptors

expressed in many tissues

homodimer

JAK-STAT pathway

Hyperprolactinemia: major causes

prolactinoma

medications blocking D₂ semesters (less negative feedback)

Reduced PRL elimination (renal failure, liver insufficiency)

Hyperprolactinemia: symptoms

Tumor-linked: headache, visual disturbance, hypopituitarism

Typical symptoms: fertility problems, amenorrhea, galactorrhea, sexual dysfunction, osteoporosis, possible increased breast cancer risk

Dopamine receptor agonists: clinical uses

hyperprolactinemia: decreased pituitary secretion of prolactin - oral or vaginal

Acromegaly: decreased GH secretion (less effective) - oral

Parkinson’s Disease: dopaminergic effects on CNS motor control and behavior - oral

Dopamine receptor agonists: medications

Bromocriptine (t ½ = 2-7h): twice daily, can cause hypotension

Cabergoline (t ½ = 65): twice weekly

PollEv: Which of the following hormones is nicknamed as a “love hormone” or a “cuddle chemical”?

oxytocin

Oxytocin

posterior pituitary hormone

used for labor/lactation indications

Oxytocin: release

induced by cervical/vaginal dilation and nipple stimulation

Oxytocin: uterine smooth muscle

produces contraction; sensitivity to the hormone is increased by estrogen

low doses: increase the frequency and force of uterine contraction

high doses: sustained contraction (bad)

Oxytocin: mammary gland

induces duct contraction which causes milk ejection

lactation cannot occur without oxytocin and prolactin

Oxytocin: indications

induce labor when early vaginal delivery is necessary

augment labor that is protracted

control postpartum uterine hemorrhage

Oxytocin: administration

IV with an infusion pump or IM injection

- proper monitoring needed. excessive uterine stimulation can lead to fetal stress

Atosiban

oxytocin antagonist

Outside US: used to inhibit/delay preterm labor

not FDA approved in US

PollEv: oxytocin has been used in preclinical trials to test whether it is effective in which of the following conditions?

All, but has not been proven effective

Vasopressin (ADH)

released by hypothalamic neurons from the posterior pituitary

activates V1 receptors on blood vessels (vasoconstriction) and V2 receptors in the kidney (increase water reabsorption)

Vasopressin: release

released in response to

- falling BP detected by baroreceptors on aortic arch and carotid sinus

- rising plasma osmolarity detected by osmoreceptors on neurons

ADH deficiency

Diabetes insipidus

ADH: water re-absorption

ADH activates V2 receptors

increase in cAMP and PKA activity

phosphorylates proteins involved in trafficking

promote expression of aquaporin2 on the luminal membrane

Diabetes insipidus

caused by deficient ADH secretion

neurogenic (pituitary) DI is caused by inability of the posterior pituitary to secrete ADH

symptoms: hypernatremia, polyuria, polydipsia

Diabetes Insipidus: Treatment

desmopressin (synthetic analog of vasopressin)

long t ½ = about 2 hours

IV, SC, intranasal, oral

adverse effects: GI disturbance, headache, hyponatremia

Syndrome of inappropriate ADH (SIADH)

disease with excessive ADH secretion

common cause: ectopic secretion of ADH by small cell carcinoma of the lungs

symptoms: hypertension, water over-retention, hyponatremia

SIADH: treatment

Conivaptan (IV infusion) or Tolvaptan (oral tabs)

competitive antagonists

tolvaptan - more selective for V2 receptors (kidney) than V1 receptors (blood vessels)

adverse effects: GI upset, polyuria, polydipsia

PollEv: Conivaptan, a vasopressin antagonist, is useful in treating hyponatremia by which of the following mechanisms?

increasing the renal excretion of water

PollEv: which of the following best describes the mechanism of action of desmopressin in the treatment of central diabetes insipidus?

increased expression of aquaporin2 channels in the renal collecting duct cell membranes

PollEv: Nephrogenic diabetes insipidus is a disease caused by genetic deficiency of V2 receptors in the kidney. a) what is a typical symptom? b) Is desmopressin an effective treatment?

a) Polyuria b) No

PollEv: hyperprolactinemia can be treated with a(n)

dopamine agonist