Contents · 12 sections
In a nutshell. Hormones are signaling molecules produced by endocrine glands and the diffuse neuroendocrine system. Chemically, they are classified into peptide hormones (insulin, PTH, GH — rapid effects via membrane receptors), steroid hormones (cortisol, aldosterone, sex hormones — slow effects via nuclear receptors and transcription), thyroid hormones (T3/T4 — nuclear receptors, basal metabolism), and amino acid derivatives (catecholamines via G-proteins; melatonin). Regulation occurs via negative feedback through the hypothalamic-pituitary axis.
1. General characteristics
- Synthesized in endocrine glands or the diffuse neuroendocrine system (APUD cells).
- Act at a distance (endocrine), locally (paracrine), or on the cell of origin (autocrine).
- Blood concentrations: 10⁻¹² — 10⁻⁶ mol/L (very low).
- Half-life ranges from seconds (catecholamines) to hours or days (thyroxine — 7 days).
- Transport: water-soluble hormones circulate freely in plasma; steroid/thyroid hormones are bound to transport proteins (TBG, CBG, SHBG, albumin).
2. Chemical Classification
| Class | Examples | Synthesis | Receptor |
|---|---|---|---|
| Peptide/protein hormones | Insulin, glucagon, PTH, GH, prolactin, TSH, ACTH, ADH, oxytocin | Ribosomes → prohormone → proteolysis | Membrane (G-protein, tyrosine kinase) |
| Steroid hormones | Cortisol, aldosterone, testosterone, estradiol, progesterone, vitamin D | Derived from cholesterol in mitochondria + SER | Nuclear |
| Thyroid hormones | T3 (triiodothyronine), T4 (thyroxine) | Iodination of tyrosine residues on thyroglobulin | Nuclear |
| Amino acid derivatives | Epinephrine, norepinephrine, dopamine, serotonin, melatonin, histamine | Decarboxylation of amino acids | Membrane (G-protein) |
| Eicosanoids | Prostaglandins, leukotrienes, thromboxanes | Derived from arachidonic acid | Local, G-protein-coupled |
3. Mechanisms of Action
Membrane receptors
- G-protein-coupled (7-transmembrane): epinephrine (α, β), glucagon, ACTH, TSH, vasopressin.
- Second messengers: cAMP (Gs ↑, Gi ↓), IP3/DAG (Gq), Ca²⁺.
- Tyrosine kinase-linked receptors: insulin, IGF-1, GH (via JAK/STAT).
- Guanylyl cyclase-linked receptors: atrial natriuretic peptide (ANP).
Nuclear receptors
- Lipophilic hormones cross the cell membrane and bind to receptors in the cytoplasm/nucleus.
- The receptor-ligand complex binds to DNA (hormone response element) → alters transcription.
- Effects are slow (hours to days) but sustained.
- Examples: glucocorticoids, mineralocorticoids, sex hormones, thyroid hormones, vitamin D, retinoids.
4. Hypothalamic-Pituitary Axis
- Hypothalamus → releasing/inhibiting hormones → anterior pituitary.
- TRH → TSH → T3/T4 (feedback loops acting on the hypothalamus and pituitary).
- CRH → ACTH → cortisol (circadian rhythm, peak at 6–8 AM).
- GnRH → LH/FSH → sex hormones.
- GHRH → GH → IGF-1 (somatomedin C).
- Dopamine (inhibitory) → ↓ prolactin; oxytocin and ADH — direct secretion into the posterior pituitary.
5. Feedback
- Negative feedback — the primary mechanism: the final hormone inhibits higher regulatory levels.
- Short-loop feedback — a pituitary hormone inhibits the hypothalamus.
- Long-loop feedback — a peripheral hormone inhibits the pituitary and hypothalamus.
- Ultrashort-loop feedback — within the gland itself.
- Positive feedback — rare: estrogen surge prior to ovulation → ↑ LH surge.
6. Pancreatic Hormones
- Insulin (β-cells): ↓ glucose via ↑ GLUT4 uptake in muscle and adipose tissue, ↑ glycogenesis, ↓ gluconeogenesis.
- Glucagon (α-cells): ↑ glucose via glycogenolysis and gluconeogenesis in the liver.
- Somatostatin (δ-cells): inhibits insulin, glucagon, GH, TSH.
- Pancreatic polypeptide (PP cells): regulates GI tract and digestion.
7. Adrenal cortex hormones
- Zona glomerulosa — aldosterone (Na⁺ reabsorption, K⁺ secretion; regulated by RAAS, K⁺).
- Zona fasciculata — cortisol (gluconeogenesis, anti-inflammatory, catabolic effects; circadian rhythm).
- Zona reticularis — DHEA and androstenedione (weak androgens).
- Adrenal medulla — epinephrine and NE (sympathoadrenal system).
- 11β-HSD2 in the kidneys protects the mineralocorticoid receptor from cortisol; its deficiency causes syndrome of apparent mineralocorticoid excess.
8. Thyroid gland
- T4 (thyroxine) — main secreted form (93 %); T3 — active form (7 %, mostly converted from T4 in tissues).
- Synthesis: iodination of tyrosine on thyroglobulin (TPO).
- Effects: ↑ basal metabolic rate, ↑ thermogenesis (UCP1), ↑ sensitivity to catecholamines.
- Regulation: TRH → TSH → T4/T3; negative feedback to hypothalamus and pituitary gland.
- Calcitonin (C-cells) — ↓ blood Ca²⁺ (marker of medullary thyroid cancer).
9. Sex hormones
- Estrogens (estradiol — predominant in women of reproductive age): ↑ endometrial proliferation, development of secondary sex characteristics.
- Progesterone: secretory phase of the endometrium, maintenance of pregnancy.
- Testosterone: libido, muscle mass, spermatogenesis; DHT — predominant in tissues.
- Inhibin — inhibits FSH.
- AMH (anti-Müllerian hormone) — marker of ovarian reserve, embryonic regression of Müllerian ducts in males.
10. Calcium-phosphate metabolism
- PTH (parathyroid hormone, parathyroid chief cells): ↑ blood Ca²⁺ via bone mobilization, renal reabsorption, vitamin D activation.
- Calcitriol (1,25-(OH)₂-D3): ↑ intestinal absorption of Ca²⁺ and P.
- Calcitonin: ↓ Ca²⁺ (minor effect in humans).
- FGF-23 (from osteocytes): ↓ renal phosphate reabsorption.
11. Laboratory diagnostics
- Primary TSH — initial thyroid screening (0.4–4.0 mIU/L).
- Free T4, T3 — indicated if TSH is abnormal.
- Anti-TPO, Anti-Tg, TRAb — autoimmune thyroid disorders.
- Morning cortisol + ACTH + 1 mg dexamethasone suppression test — Cushing's syndrome.
- Aldosterone/renin ratio (ARR) — primary hyperaldosteronism (Conn's syndrome).
- hCG — pregnancy, trophoblastic tumors.
- Prolactin — prolactinoma (> 200 ng/mL).
- IGF-1 — acromegaly screening; oral glucose tolerance test with GH measurement — confirmation.
- PTH + ionized Ca²⁺ + 25-(OH)-D — parathyroid evaluation.
12. FAQ
Why do steroid hormones act slowly?
They work by altering transcription — the effect manifests through the synthesis of new proteins (hours to days). Peptide hormones act via pre-existing proteins (seconds to minutes).
How does insulin lower blood glucose?
Binds to receptor → tyrosine kinase → GLUT4 translocation to the membrane of muscle and adipocytes → ↑ glucose uptake; + activation of glycogen synthase and suppression of gluconeogenesis.
Why does TSH rise in primary hypothyroidism?
Negative feedback: ↓ T4 → pituitary gland "perceives" this as a need to stimulate the thyroid → ↑ TSH. In secondary (pituitary) hypothyroidism, TSH is ↓ or normal.
What is the difference between endocrine and paracrine effects?
Endocrine — hormone travels via blood to a distant target cell. Paracrine — affects neighboring cells (somatostatin in islets). Autocrine — affects the same cell that secreted the hormone (IL-2 in T cells).
Why does cortisol peak in the morning?
Circadian rhythm — peak at 6–8 AM, nadir at 10–12 PM. Regulated by ACTH and, more fundamentally, the suprachiasmatic nucleus of the hypothalamus (master clock).
See also: Diabetes mellitus · Hypothyroidism and thyrotoxicosis · Cushing's syndrome · Hyperaldosteronism · Endocrinology catalog