Endocrine System

The endocrine system communicates through hormones — chemical messengers synthesised and released by endocrine glands into the bloodstream — that travel to distant target tissues and regulate physiology over seconds to days. Together with the nervous system (which communicates over milliseconds via synapses), the endocrine system coordinates homeostasis, metabolism, growth, reproduction, water balance, and the body's response to stress.

The major endocrine glands and their hormones form a hierarchically organised system with the hypothalamus and pituitary at the apex. The hypothalamus integrates neural signals from the cortex, limbic system, and brainstem with blood-borne signals (hormones, glucose, cytokines) and releases short-range releasing hormones (CRH, TRH, GnRH, GHRH, dopamine) into the hypothalamic-pituitary portal blood supply. These act on the anterior pituitary to stimulate release of tropic hormones (ACTH, TSH, GH, FSH, LH, prolactin) into the systemic circulation, which in turn act on peripheral endocrine glands (adrenal cortex, thyroid, gonads) to release effector hormones (cortisol, thyroxine, oestrogen, testosterone). These effector hormones act widely on target tissues and feed back to regulate the axis.

The adrenal glands exemplify the neuroendocrine interface. The adrenal cortex (mesodermal origin, ~80–90%) produces steroid hormones: aldosterone (zona glomerulosa, sodium balance), cortisol (zona fasciculata, the primary stress glucocorticoid), and adrenal androgens (zona reticularis). The adrenal medulla (neural crest origin, ~10–20%) is effectively a modified sympathetic ganglion — receiving preganglionic cholinergic innervation and secreting catecholamines (adrenaline ~80%, noradrenaline ~20%) directly into the bloodstream: the hormonal limb of the fight-or-flight response.

The body has two major stress response axes. The sympatho-adrenal medullary (SAM) axis, described by Walter Cannon (1932), is immediate: sympathetic activation + adrenal medulla catecholamines prepare the body for action within seconds, peaking within 30 seconds. The hypothalamic-pituitary-adrenocortical (HPA) axis is slower: CRH → ACTH → cortisol peaks at 20–30 minutes, with effects lasting hours. Cortisol mobilises energy (gluconeogenesis, lipolysis), suppresses immunity, and potentiates catecholamine actions. Negative feedback via glucocorticoid receptors (GR) in the hypothalamus, pituitary, and hippocampus limits the HPA response. Chronic stress impairs hippocampal GR expression, disrupting this feedback and leading to chronically elevated cortisol — with consequences including hippocampal atrophy, immune dysregulation, metabolic syndrome, and depression (McEwen, 2007).