The endocrine system is a chemical communication network of ductless glands that secrete hormones directly into the bloodstream. Unlike the nervous system (which uses electrical signals and neurotransmitters for rapid, localised effects), endocrine signalling is slower, travels via blood, and produces longer-lasting, body-wide effects. The two systems are integrated through the hypothalamus, which receives neural inputs and converts them into hormonal outputs, making it the master coordinator of chemical coordination.
Hypothalamus-Pituitary Axis
The hypothalamus produces releasing hormones (GnRH, CRH, TRH, GHRH) that travel through the hypophyseal portal blood system to stimulate specific cell types in the anterior pituitary. Inhibiting hormones (somatostatin — inhibits GH and TSH; PIF/dopamine — inhibits prolactin) provide tonic suppression. The anterior pituitary (adenohypophysis) responds by secreting six key tropic hormones, remembered by the mnemonic FLAT PG: FSH, LH, ACTH, TSH, Prolactin, and GH. These tropic hormones act on peripheral glands (thyroid, adrenal cortex, gonads) to drive their hormone production.
Regulation operates via negative feedback: rising levels of the end-hormone (e.g., T4, cortisol) inhibit both the hypothalamic releasing hormone and the pituitary tropic hormone, maintaining homeostasis. The one notable exception is the mid-cycle oestrogen surge, which generates positive feedback on the pituitary, causing the LH surge that triggers ovulation.
The posterior pituitary (neurohypophysis) does not produce hormones. It stores and releases ADH (vasopressin — promotes water reabsorption in the renal distal convoluted tubule and collecting duct via aquaporin insertion) and oxytocin (drives uterine contractions during labour and milk ejection during breastfeeding). Both are synthesised by neurosecretory cells in the hypothalamus (ADH in the supraoptic nucleus; oxytocin in the paraventricular nucleus) and transported along axons to the posterior pituitary. This is the most frequently tested NEET distinction in this chapter.
Thyroid and Parathyroid
The thyroid gland produces T3 (triiodothyronine, 3 iodine atoms) and T4 (thyroxine, 4 iodine atoms), both requiring dietary iodine. T4 is the primary secretory product but is a prohormone; peripheral deiodination yields the more active T3 (3–5× more potent). Both increase basal metabolic rate (BMR), promote growth, and support nervous system development. The thyroid also produces calcitonin from parafollicular C-cells, which lowers blood calcium by inhibiting osteoclasts and reducing renal calcium reabsorption.
The four parathyroid glands (embedded in the thyroid's posterior surface) produce PTH, which raises blood calcium through three mechanisms: (1) stimulating osteoclasts to resorb bone, (2) increasing renal calcium reabsorption in the DCT, and (3) activating renal 1-alpha-hydroxylase to produce calcitriol (active vitamin D), which enhances intestinal calcium absorption. PTH and calcitonin are a canonical antagonistic pair for calcium homeostasis.
Adrenal Gland
The adrenal cortex has three zones with distinct steroid-producing profiles (mnemonic: GFR = Salt, Sugar, Sex from outer to inner): zona glomerulosa (aldosterone — a mineralocorticoid that promotes Na+ reabsorption and K+ secretion in the DCT, increasing blood volume and blood pressure), zona fasciculata (cortisol — a glucocorticoid that stimulates gluconeogenesis, is anti-inflammatory via nuclear receptor-mediated gene suppression, immunosuppressive, and promotes the stress response), and zona reticularis (androgens — minor sex corticoids such as DHEA). The adrenal medulla, derived from neural crest cells and innervated by preganglionic sympathetic fibres, secretes catecholamines: adrenaline (80%; increases heart rate, blood glucose, bronchodilation) and noradrenaline (20%; primarily vasoconstriction). Together they mediate the fight-or-flight response.
Pancreatic Islets
The islets of Langerhans in the pancreas contain three cell types: alpha (α) cells producing glucagon (hyperglycaemic — promotes glycogenolysis and gluconeogenesis in the liver), beta (β) cells producing insulin (hypoglycaemic — promotes cellular glucose uptake via GLUT4, glycogenesis, and lipogenesis), and delta (δ) cells producing somatostatin (inhibits both insulin and glucagon secretion). Insulin and glucagon are the primary antagonistic pair for blood glucose regulation. Insulin is the only hypoglycaemic hormone in the body.
Hormone Mechanisms of Action
Peptide hormones (insulin, GH, ADH, FSH, LH, ACTH, PTH, calcitonin, glucagon, oxytocin) are water-soluble and cannot cross the lipid bilayer. They bind surface membrane receptors, activating G-protein coupled pathways (adenylyl cyclase → cAMP → protein kinase A cascade) or receptor tyrosine kinases (insulin receptor), producing rapid but transient effects (seconds to minutes).
Steroid hormones (cortisol, aldosterone, androgens, oestrogen, progesterone, testosterone) and thyroid hormones (T3, T4) are lipid-soluble. They cross the plasma membrane, bind intracellular receptors (cytoplasmic or nuclear), and the hormone-receptor complex directly modulates gene transcription — producing slower but sustained effects (hours).
Major Disorders
Endocrine disorders arise from hypo- or hypersecretion. GH deficiency in childhood → pituitary dwarfism; GH excess before plate fusion → gigantism; GH excess after plate fusion → acromegaly (enlarged extremities, no height increase). Hypothyroidism in children → cretinism (irreversible stunted growth and mental retardation); hypothyroidism in adults → myxoedema (puffy face, low BMR). Hyperthyroidism (Graves' disease) → exophthalmos, weight loss, high BMR. Adrenal cortex hypofunction → Addison's disease (hypoglycaemia, weakness, hyperpigmentation from excess ACTH/MSH). Adrenal cortex hyperfunction → Cushing's syndrome (moon face, buffalo hump, hyperglycaemia). Type 1 DM = autoimmune β-cell destruction (insulin-dependent); Type 2 DM = insulin resistance (initially non-insulin-dependent). Diabetes insipidus = ADH deficiency (polyuria with normal blood glucose). PTH deficiency → hypocalcaemia → tetany.