Pituitary & Hypothalamus — Pituitary Hormones

Pituitary

• HPA describes complex feedback loops between these endocrine organs
  • Shortloop feedback: -ve feedback from pituitary on the hypothalamus e.g. thyroxin inhibiting TSH release
  • Long-loop feedback: -ve feedback from pituitary target gland (e.g. thyroid, adrenal, gonads) on the hypothalamus e.g. cortisol inhibiting CRH (as well as ACTH) release
• Pituitary hormones
  • Anterior pituitary
    • Secretes 6 hormones in response to hypothalamic endocrine stimulus
    • Stimulating hormones:
      • Act at another gland
      • Includes: ACTH, TSH, FSH, LH
    • Directly acting hormones
      • Include: GH, prolactin
  • Posterior pituitary
    • ADH
    • Oxytocin

Control of secretion of hormones from the posterior pituitary

ADH:

• Nonapeptide (9 a.a.) synthesized 1°ly in cell body of SON (some also in PVN) of the
  hypothalamus → transported to posterior pituitary via infundibulum where it is stored
• It is secreted in response to:
  • ↑ plasma osmolality (Major determinant)
    • Detected by osmoreceptors (in anterior hypothalamus near SON/PVN)
    • Very sensitive (detects 1% change in osmolality) → threshold for ADH
      release is 280 mosm/kg (slightly less than normal plasma osmolality) →
      steep linear rise > 290 mosm/kg
  • Non-osmotic stimuli:
    • Haemodynamic changes
      • ↓ PV → ↓ MAP that is sensed by baroreceptors (mainly lowpressure BR in atrium) → cause ↑ ADH release
      • ↓ sensitivity cf. osmotic stimuli (detects 5-10% change in PV)
      • BUT very potent → overrides osmoreceptors (in terms of control
        of ADH secretion) when there are LARGE changes in PV!!!
    • ↑ AII
    • Pain
    • Nausea/vomiting (powerful stimuli)
    • Exercise
    • Drugs (↑ release – morphine, nicotine, barbiturate; ↓ release – EtOH)
• Effects:
  • V1 receptor (GPCR via Gq → activates PLC to ↑ IP3 → ↑ IC [Ca2+] → smooth muscle contraction) → this causes:
    • Contraction of vascular SM cells (potent vasoconstrictor effect) → ↑ TPR and MAP
    • Renal afferent arteriolar constriction and contraction of renal mesangial cells → ↓ GFR/RBF
    • Platelet aggregation and degranulation
  • V2 receptor (GPCR via Gs → activates AC to ↑ cAMP → activates PKA) → this causes:
    • Upregulates insertion of apical membrane AQP2 (stored in vesicles) in principal cells of CCD and MCD → ↑ H2O permeability → ↑ H2O reabsorption into hypertonic medullary interstitium (across BLM AQP3 and 4) → causes ↓ plasma osmolality (and ↑ urine concentration)
    • Upregulates “urea transporters” in principal cells of inner MCD → ↑ permeability to urea → ↑ urea absorption to maintain ↑ medullary osmolality (strengthens CCM)
    • ↑ Na+ reabsorption and K+
      secretion by principal cells of CCD
    • ↑ CF VIII release by vascular endothelium
  • Other effects:
    • CNS → promotes memory, learning, attention and concentration
    • ACTH release form anterior pituitary gland
• ADH’s effect is very short-lived → short t ½ ~ 20 mins (rapidly inactivated by tissue peptidases → excreted by liver and kidney)

Oxytocin

• Nonapeptide (9 a.a.) synthesised 1°ly in cell body of PVN (some also in SON) of the hypothalamus → transported via infundibulum to be stored in posterior pituitary gland
• Control of secretion – (i) ↑ release in response to → cholinergic stimulation, (ii) ↓ release in response to → β-adrenergic activity, EtOH, enkephalins
• Effects:
  • Ejection of milk – Somatic touch stimulation of nipple (Ie. suckling) stimulates “let-down reflex” → cause oxytocin release to induce contraction of myoepithelium of lactating mammary glands → milk secretion
  • Myometrial contraction of pregnant uterus → during late pregnancy, a neuroendocrine reflex loop causes ↑ both oxytocin secretion and oxytocin receptor population → role in inducing labour/delivery
  • Uterine secretion/contractions during coitus → facilitates propulsion of semen to fallopian tubes
  • Various behavioural effects

Bianca / Kerr 2016

Kerr 2016

Answer by Kerr