The Endocrine System

Principles of Endocrine Signalling

The endocrine system coordinates body functions through chemical messengers — hormones — secreted into the bloodstream and acting on distant target cells. Hormones differ from neural signals in their speed (slower, seconds to days), duration (longer-lasting), and range (body-wide). The endocrine and nervous systems are deeply integrated: the hypothalamus serves as the master link, translating neural signals into hormonal output via the pituitary gland.

Hormone Classes

Peptide and protein hormones (e.g., insulin, GH, TSH, PTH) are water-soluble, cannot cross cell membranes, and bind to surface receptors coupled to second-messenger cascades (cAMP, IP₃/DAG, RTK). They are synthesised as prepro-hormones, processed in the ER and Golgi, and stored in secretory granules for rapid release.

Steroid hormones (e.g., cortisol, aldosterone, oestrogen, testosterone, calcitriol) are lipid-soluble, diffuse across cell membranes, and bind intracellular receptors that act as transcription factors, altering gene expression with a delay of hours. Derived from cholesterol.

Amine hormones include catecholamines (adrenaline, noradrenaline — act at surface receptors, fast) and thyroid hormones (T₃, T₄ — act at nuclear receptors like steroids, slow).

Hypothalamic-Pituitary Axis

The hypothalamus produces releasing and inhibiting hormones that travel via the hypothalamo-hypophyseal portal system to the anterior pituitary, regulating the secretion of its six hormones: GH, TSH, ACTH, FSH, LH, and prolactin. The posterior pituitary (neurohypophysis) stores and releases ADH (vasopressin) and oxytocin, synthesised by hypothalamic neurons. Negative feedback from target-organ hormones (e.g., cortisol inhibits CRH and ACTH release) regulates the axis.

The Thyroid Gland

The thyroid gland synthesises T₃ (triiodothyronine, the active form) and T₄ (thyroxine, the prohormone) from tyrosine and iodine. TSH from the anterior pituitary stimulates follicular cell uptake of iodide (via NIS), thyroglobulin synthesis, thyroid peroxidase activity (coupling and organification), and hormone release. T₃ and T₄ are transported bound to TBG (thyroxine-binding globulin); only free hormone is active. T₄ is deiodinated peripherally to T₃ (active) or reverse T₃ (rT₃, inactive). Effects of thyroid hormones: increased BMR, thermogenesis, cardiac output, gut motility, and normal neural development in the fetus. Hypothyroidism (low T₃/T₄) presents with fatigue, cold intolerance, weight gain, bradycardia, and myxoedema. Hyperthyroidism presents with weight loss, heat intolerance, tachycardia, fine tremor, and exophthalmos (in Graves disease — TSH receptor autoantibodies).

The Adrenal Glands

The adrenal cortex (outer, from mesoderm) has three zones: zona glomerulosa (mineralocorticoids — aldosterone, regulated by RAAS and K⁺), zona fasciculata (glucocorticoids — cortisol, regulated by ACTH), and zona reticularis (androgens — DHEA). Cortisol is the principal stress glucocorticoid: it raises blood glucose (gluconeogenesis, protein catabolism), has anti-inflammatory effects (inhibits phospholipase A₂, reduces cytokine production), and suppresses the immune response. Cortisol secretion follows a circadian rhythm (peak in early morning). Excess cortisol → Cushing syndrome (moon face, central obesity, purple striae, hypertension, diabetes).

The adrenal medulla (inner, from neural crest) secretes adrenaline (epinephrine, ~80%) and noradrenaline — the catecholamine "fight-or-flight" response. Effects include tachycardia, bronchodilation, glycogenolysis, and lipolysis via β-adrenergic receptors.

Pancreatic Hormones

The islets of Langerhans contain: α-cells (glucagon — raises blood glucose via glycogenolysis and gluconeogenesis), β-cells (insulin — lowers blood glucose via GLUT4 upregulation, glycogen synthesis, lipogenesis), and δ-cells (somatostatin — inhibits both insulin and glucagon). Type 1 DM: autoimmune destruction of β-cells. Type 2 DM: insulin resistance followed by β-cell failure.