The Endocrine System

The endocrine system coordinates long-term physiological processes through chemical messengers called hormones, which are secreted into the bloodstream and act on distant target cells bearing specific receptors. Unlike the nervous system's millisecond signalling, endocrine responses unfold over minutes to hours and regulate metabolism, growth, reproduction, and homeostasis.

The hypothalamus-pituitary axis is the master regulator of endocrine function. The hypothalamus synthesises releasing and inhibiting hormones that travel via the hypophyseal portal blood system to the anterior pituitary, where they stimulate or suppress the release of tropic hormones. These tropic hormones then act on peripheral glands. For example, thyrotropin-releasing hormone (TRH) → thyroid-stimulating hormone (TSH) → thyroid hormones (T3/T4). Corticotropin-releasing hormone (CRH) → adrenocorticotropic hormone (ACTH) → cortisol. Growth hormone-releasing hormone (GHRH) → growth hormone (GH) → IGF-1. Gonadotropin-releasing hormone (GnRH) → LH and FSH → sex steroids. The posterior pituitary does not produce hormones itself; it stores and releases oxytocin and antidiuretic hormone (ADH/vasopressin), which are synthesised by hypothalamic neurons.

Negative feedback is the dominant regulatory mechanism: rising hormone levels inhibit further hormone release at the hypothalamic and pituitary levels. For example, elevated cortisol suppresses CRH and ACTH release, preventing adrenal hyperstimulation. Positive feedback is rare but exemplified by the LH surge at mid-cycle — rising oestrogen from a mature ovarian follicle stimulates a large LH pulse that triggers ovulation.

The thyroid gland produces T3 (triiodothyronine) and T4 (thyroxine). Iodide is actively transported into follicular cells and incorporated into thyroglobulin. T4 is the primary secreted form; peripheral deiodination converts T4 to the more active T3. Thyroid hormones increase basal metabolic rate, stimulate protein synthesis, promote normal CNS development in the fetus, and regulate cardiac output. Hypothyroidism causes fatigue, weight gain, cold intolerance, and bradycardia; hyperthyroidism (e.g., Graves' disease, TSH-receptor autoantibodies) causes weight loss, heat intolerance, tachycardia, and tremor.

The adrenal glands have two functionally distinct regions. The adrenal cortex secretes steroid hormones: cortisol (zona fasciculata — glucocorticoid, stress response: gluconeogenesis, immunosuppression, anti-inflammatory); aldosterone (zona glomerulosa — mineralocorticoid, Na+ retention, K+ excretion); and dehydroepiandrosterone (DHEA; zona reticularis — weak androgen). The adrenal medulla secretes catecholamines (adrenaline ~80%, noradrenaline ~20%) in response to sympathetic stimulation, mediating the acute fight-or-flight response.

The pancreas contains the islets of Langerhans. Beta cells secrete insulin in response to elevated blood glucose (via GLUT2 sensing and ATP-sensitive K+ channel closure). Insulin promotes glucose uptake (GLUT4 translocation in muscle and adipose), glycogen synthesis, and protein synthesis while suppressing gluconeogenesis. Type 1 diabetes results from autoimmune beta-cell destruction; type 2 from insulin resistance and relative secretory failure. Alpha cells secrete glucagon, which raises blood glucose via hepatic glycogenolysis and gluconeogenesis — the counter-regulatory hormone to insulin.