The Endocrine System, Hormones & Stress Response

All 10 Terms & Definitions

Endocrine signalling

Communication via hormones released into the bloodstream that travel to distant target tissues. Key properties: slow onset (seconds to hours, limited by circulation time), long duration (minutes to days), wide distribution (all tissues exposed but only those with appropriate receptors respond), and concentration-dependent effects that can be amplified by receptor density and signalling cascades. Contrasts with neural signalling (milliseconds, highly targeted, brief).

Hormone types

Hormones are classified by chemical structure: (1) Peptide/protein hormones (e.g., insulin, ACTH, GH): water-soluble, act on surface receptors, rapid onset via second-messenger cascades; (2) Steroid hormones (e.g., cortisol, aldosterone, oestrogen, testosterone): lipid-soluble, synthesised from cholesterol, cross cell membranes and act on intracellular receptors that directly regulate gene transcription — slower but longer-lasting effects; (3) Amine hormones (e.g., adrenaline, thyroxine): derived from amino acids; adrenaline is water-soluble (surface receptors), thyroxine is lipid-soluble (nuclear receptors).

Hypothalamic-pituitary axis

The master regulatory axis of the endocrine system. Three-tier cascade: Hypothalamus (integrates neural and blood-borne signals) → releases short-range releasing/inhibiting hormones into the portal blood supply → Anterior pituitary releases tropic hormones (ACTH, TSH, GH, FSH, LH, prolactin) into systemic blood → Peripheral glands (adrenal cortex, thyroid, gonads) release effector hormones that act on target tissues and feed back to regulate the axis. The posterior pituitary (ADH, oxytocin) is regulated differently — by direct neural input from hypothalamic nuclei.

Adrenal cortex

The outer region (~80–90%) of the adrenal gland, embryologically derived from mesoderm. Three functional zones: zona glomerulosa → aldosterone (mineralocorticoid: stimulates renal Na+ reabsorption and K+ excretion, raises blood pressure; regulated by angiotensin II and plasma K+); zona fasciculata → cortisol (glucocorticoid: stress response, gluconeogenesis, immune modulation; regulated by ACTH); zona reticularis → DHEA and androstenedione (weak androgens). All cortical hormones are steroids synthesised from cholesterol.

Adrenal medulla

The inner region (~10–20%) of the adrenal gland, embryologically derived from neural crest (same lineage as sympathetic neurons) — effectively a modified sympathetic ganglion that secretes directly into blood. Chromaffin cells receive preganglionic sympathetic input (ACh on nicotinic receptors) and release catecholamines: ~80% adrenaline (epinephrine) and ~20% noradrenaline (norepinephrine) into the bloodstream. The key effector organ of the SAM axis.

Fight-or-flight response (SAM axis)

Walter Cannon's term (first used 1915; elaborated in The Wisdom of the Body, 1932) for the acute physiological response to perceived threat, mediated by the sympatho-adrenal medullary (SAM) axis. Stressor → hypothalamus/brainstem activate sympathetic preganglionic neurons → noradrenaline at target synapses (immediate, milliseconds) + adrenaline and noradrenaline from adrenal medulla into bloodstream (seconds). Effects: ↑ heart rate and cardiac output, vasoconstriction in skin and viscera, vasodilation in skeletal muscle, bronchodilation, ↑ blood glucose (glycogenolysis), pupil dilation, sweating. Peaks within 30 seconds; catecholamines cleared within minutes.

HPA axis

Hypothalamic-pituitary-adrenocortical axis: the slower, sustained arm of the stress response. Stressor → hypothalamic paraventricular nucleus releases CRH → anterior pituitary releases ACTH → adrenal cortex synthesises and releases cortisol. Cortisol peaks at 20–30 minutes; half-life ~90 minutes. Actions: gluconeogenesis and lipolysis (sustained energy), immunosuppression (reduces risk of excessive inflammation), potentiation of fear memory consolidation (amygdala), and negative feedback via glucocorticoid receptors in hypothalamus and pituitary. Chronic HPA hyperactivation causes hippocampal atrophy, immune dysregulation, and metabolic syndrome (McEwen, 2007).

Cortisol

The primary glucocorticoid produced by the adrenal cortex zona fasciculata under ACTH stimulation. Steroid hormone acting via intracellular glucocorticoid receptors (GR) that regulate gene transcription. Acute effects: mobilises energy via gluconeogenesis (new glucose from amino acids and glycerol), lipolysis, and glycogenolysis; immunosuppression (inhibits prostaglandin synthesis, reduces lymphocyte proliferation); potentiates catecholamine actions on blood vessels; enhances memory consolidation for emotional/stressful events. Chronic elevation: hippocampal neuronal atrophy, impaired memory, metabolic syndrome, depression.

Negative feedback in the HPA axis

The self-limiting mechanism that prevents sustained cortisol hypersecretion. Rising cortisol acts on glucocorticoid receptors (GR) in the hypothalamus (reduces CRH secretion) and anterior pituitary (reduces ACTH secretion), progressively turning off its own production. Fast feedback (minutes, membrane-mediated) and slow feedback (hours-days, genomic repression of CRH and POMC genes). Hippocampal GRs provide tonic inhibition of the HPA axis. Chronic stress downregulates hippocampal GRs, impairing feedback and perpetuating cortisol elevation.

Adrenaline and noradrenaline as hormones and NTs

Adrenaline (epinephrine) and noradrenaline (norepinephrine) are catecholamines (derived from tyrosine via dopamine) that function both as neurotransmitters (released at sympathetic synapses and CNS neurons, especially locus coeruleus) and as hormones (released from adrenal medulla). Same molecules, same adrenergic receptors (α1, α2, β1, β2, β3). As NTs: millisecond onset, highly localised, rapid reuptake via NET. As hormones: seconds onset, systemic, cleared by MAO/COMT/reuptake over minutes. Adrenaline has high β affinity (cardiac, bronchial); noradrenaline has high α affinity (vasoconstriction).