Endocrine Physiology: Hypothalamic-Pituitary Axis covers endocrine physiology — the hypothalamic-pituitary axis for INI CET (AIIMS PG).
Hypothalamus as Master Regulator:
- Directs pituitary via:
- Hypophyseal portal system: Primary capillary plexus → portal veins → sinusoids of anterior pituitary → delivers high-concentration hypothalamic releasing/inhibiting hormones
- Neural connection (via median eminence): Hypothalamic neurons send axons to posterior pituitary
Anterior Pituitary Hormones (Adenohypophysis) — “B-FLAT, PGa” mnemonic:
| Hormone | Target | Function |
|---|---|---|
| FSH | Gonads | Follicular development (♀), spermatogenesis (♂) |
| LH | Gonads | Ovulation, corpus luteum formation (♀); testosterone production (♂) |
| TSH | Thyroid | Thyroid growth, T₃/T₄ synthesis/release |
| ACTH | Adrenal cortex | Cortisol synthesis; androgens |
| GH | Many tissues | Growth (IGF-1 mediated); metabolic effects |
| Prolactin | Breast | Milk production (lactation) |
Hypothalamic Releasing/Inhibiting Hormones:
| Hormone | Effect on AP | Target |
|---|---|---|
| GnRH | ↑FSH + LH | Gonads |
| TRH | ↑TSH + Prolactin | Thyroid, breast |
| CRH | ↑ACTH | Adrenal cortex |
| GHRH | ↑GH | Somatotrophs |
| Somatostatin (SS) | ↓GH, ↓TSH | Somatotrophs, thyrotrophs |
| Dopamine (PIF) | ↓Prolactin | Lactotrophs |
| Oxytocin (neural) | Milk ejection | Breast, uterus |
GH (Growth Hormone):
- Actions: ↑linear growth (via hepatic IGF-1/IGF-1R); ↑protein synthesis; ↓glucose utilization (diabetogenic); ↑lipolysis
- Secretion: Pulses (largest during deep sleep — stage III/IV NREM); ↑GHRH, ↓somatostatin; ↑GHRH from exercise, stress, fasting, hypoglycemia
- GH deficiency: Children → short stature (pituitary dwarfism); Adults → ↓muscle mass, ↑adiposity
- GH excess: Children → gigantism (before epiphyseal closure); Adults → acromegaly (after closure — coarse facial features, organomegaly, insulin resistance)
- Tests: IGF-1 level (integrated GH secretion), GH stimulation test (for deficiency), GH suppression test (for excess — oral glucose load should suppress GH to <1 ng/mL; fails to suppress in acromegaly)
Prolactin:
- Secretion: Primarily inhibited by dopamine (tonic inhibition); ↑ in pregnancy (estrogen刺激 lactotrophs); TRH also stimulates
- Function: Stimulates breast development during pregnancy; initiates and maintains lactation (milk production)
- Hyperprolactinemia: Galactorrhea, amenorrhea, ↓libido, infertility; causes: prolactinoma, antipsychotics (dopamine antagonists), hypothyroidism
Posterior Pituitary (Neurohypophysis):
- Oxytocin: Suckling reflex → oxytocin release → milk ejection (let-down reflex) + uterine contraction during labor
- ADH (Vasopressin): ↑Aquaporin-2 (AQP2) channels in collecting duct → water reabsorption → ↓plasma osmolality; V1 receptors → vasoconstriction
- ADH regulation: Osmoreceptors (OVLT) — ↑plasma osmolality → ↑ADH; Baroreceptors — ↓blood volume/pressure → ↑ADH; Alcohol → ↓ADH (diuresis)
- SIADH: Syndrome of Inappropriate ADH secretion → water retention, hyponatremia; causes: small cell lung cancer, CNS disorders, pulmonary disease, drugs (carbamazepine)
- Diabetes Insipidus: ↓ADH (central) or kidney resistance (nephrogenic) → large volumes of dilute urine (polyuria, polydipsia); causes: head trauma, surgery, lithium (nephrogenic)
Feedback Loops:
- Thyroid axis: Hypothalamus (TRH) → AP (TSH) → Thyroid (T₃/T₄); T₃/T₄ feedback inhibit both
- Adrenal axis: Hypothalamus (CRH) → AP (ACTH) → Adrenal cortex (cortisol); cortisol feedback inhibits both
- Gonadal axis: Hypothalamus (GnRH) → AP (LH/FSH) → Gonads (estrogen/testosterone/inhibin); feedback in both directions
- GH axis: Hypothalamus (GHRH/SS) → AP (GH) → Liver (IGF-1); IGF-1 feedback inhibits GH
⚡ Exam Tip for INI CET (AIIMS PG): Cushing’s disease = pituitary ACTH adenoma (CRH-independent ACTH production). Cushing’s syndrome = any cause of hypercortisolism (Cushing’s disease, adrenal adenoma, ectopic ACTH, iatrogenic). Distinguish by: ACTH levels (high in pituitary/ectopic; low in adrenal), high-dose dexamethasone suppression test (suppresses in pituitary; not in ectopic or adrenal), CRH stimulation (rise in ACTH in pituitary; no response in ectopic).