General

Endocrine3 min read
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General endocrine principles

Negative feedback is the dominant control mechanism. Positive feedback is uncommon and self-amplifying; estrogen-triggered LH surge before ovulation is the classic example.

Peptide hormones are synthesized as preprohormones in rough ER, processed to prohormones, cleaved in Golgi/secretory granules and released by exocytosis.

Steroid hormones derive from cholesterol, are generally synthesized on demand and are not stored in large secretory granules. Major endocrine amines derive from tyrosine.

Hormone classExamplesStorage / transportReceptor & response
Peptide/proteinInsulin, GH, ACTH, PTH, ADHStored in granules; usually circulate freelyCell membrane; second messengers; rapid onset
SteroidCortisol, aldosterone, vitamin DMade on demand; often protein-bound in plasmaIntracellular/nuclear; gene transcription; slower but longer-lasting
AmineT3/T4, epinephrine, norepinephrineThyroid hormone stored in colloid; catecholamines in vesiclesT3/T4: nuclear and slower; catecholamines: membrane receptors and rapid

Receptor regulation

Down-regulation: prolonged hormone exposure decreases receptor number/affinity and reduces responsiveness.

Up-regulation: increased receptor number/affinity makes the target more sensitive.

Cell signaling and second messengers

PathwaySequenceHigh-yield examples
Gs → cAMP → PKAReceptor activates adenylate cyclase; ATP becomes cAMP; PKA phosphorylates proteinsACTH, TSH, LH, FSH, CRH, GHRH, glucagon, PTH, calcitonin, hCG, ADH-V2
Gq → IP3/DAG → Ca²⁺/PKCPhospholipase C produces IP3 and DAG; IP3 releases intracellular Ca²⁺; DAG activates PKCGnRH, TRH, angiotensin II, ADH-V1, oxytocin, α1 receptors
Tyrosine kinaseReceptor dimerization/autophosphorylation activates intracellular proteinsInsulin, IGF-1
Intracellular/nuclear receptorHormone enters cell; receptor complex regulates DNA transcription and protein synthesisCortisol, aldosterone, thyroid hormone, vitamin D
cGMPGuanylate cyclase increases cGMPANP, nitric oxide
Ca²⁺–calmodulinIncreased intracellular calcium binds calmodulin and mediates cellular responseCa²⁺-dependent secretion and smooth-muscle responses
  • G proteins are inactive with GDP bound and active with GTP bound. Intrinsic GTPase converts GTP back to GDP and terminates signaling.
  • Phosphodiesterase breaks cAMP into 5′-AMP; inhibiting phosphodiesterase prolongs cAMP signaling.
  • Water-soluble hormones usually bind membrane receptors. Lipid-soluble hormones generally enter cells and regulate transcription.

Hypothalamus and pituitary

Structure / hormoneKey factsMCQ association
Anterior pituitaryGH, prolactin, TSH, LH, FSH, ACTH; regulated by hypothalamic releasing/inhibiting hormones via portal bloodDerived from Rathke pouch/oral ectoderm
Posterior pituitaryStores and releases ADH and oxytocin synthesized in hypothalamusNeuroectoderm; does not synthesize these hormones
TSH, LH, FSH, hCGGlycoproteins with the same α-subunit; different β-subunits confer specificityShared α-subunit
ACTH, MSH, β-lipotropin, β-endorphinDerived from pro-opiomelanocortin (POMC)POMC precursor

Posterior pituitary

HormoneOrigin in hypothalamusReceptor / mechanismActions & regulation
ADH (vasopressin)Supraoptic nucleusV2: Gs–cAMP → AQP2 insertion in collecting-duct principal cells. V1: Gq/IP3/Ca²⁺ → vasoconstriction.Increases water reabsorption. Increased by high plasma osmolality, volume contraction, pain, nausea, hypoglycemia, nicotine and opiates. Decreased by low osmolality, ethanol and ANP.
OxytocinParaventricular nucleusGq/IP3/Ca²⁺Suckling causes milk ejection via myoepithelial contraction; also contracts uterus. Cervical dilation and orgasm can stimulate release. Used to induce labour and reduce postpartum bleeding.

Pituitary traps: ADH is made in the supraoptic nucleus and oxytocin in the paraventricular nucleus; both are stored/released by the posterior pituitary. Prolactin is the anterior pituitary hormone tonically inhibited by dopamine: stalk interruption can increase prolactin while reducing other anterior pituitary output.

Cell stainingHormones
Basophils FSH, LH, ACTH, TSH
AcidophilsGH and prolactin