Physiology chapters
How hormones work
The chemical types of hormone, how water-soluble and lipid-soluble hormones travel and act, receptors and second messengers, feedback control, permissive action, down-regulation, and the general patterns of endocrine disease.
- Hormones are peptides/proteins, steroids or amines; water-soluble hormones travel free and act on cell-surface receptors with second messengers; lipid-soluble hormones (steroids, thyroid) travel bound to proteins and act on intracellular receptors to change gene transcription.
- Only the free fraction is active; binding proteins act as a reservoir and lengthen half-life.
- Most hormones are controlled by negative feedback; permissive action (e.g. cortisol for catecholamines) and down-regulation of receptors modify responses.
On this page
Overview
Hormones are chemical messengers released into the blood by endocrine glands. They act on target cells that have the right receptors, often far away.
Understanding the general rules (hormone type, transport, receptor and control) makes each gland much easier to learn.
Chemical types
| Type | Examples | Soluble in |
|---|---|---|
| Peptides and proteins | Insulin, glucagon, ADH, oxytocin, GH, prolactin, ACTH, PTH, calcitonin; glycoproteins TSH, FSH, LH, hCG | Water |
| Steroids (from cholesterol) | Cortisol, aldosterone, testosterone, oestrogen, progesterone, active vitamin D | Lipid |
| Amines (from tyrosine) | Catecholamines (adrenaline, noradrenaline, dopamine) | Water |
| Thyroid hormones (T3, T4) | Lipid (act like steroids) |
Thyroid hormones are amines by origin but behave like steroids: they are lipid-soluble, protein-bound and act on nuclear receptors.
Water-soluble vs lipid-soluble hormones
| Feature | Water-soluble (peptides, catecholamines) | Lipid-soluble (steroids, thyroid) |
|---|---|---|
| Storage | Stored in vesicles, released on demand | Not stored (except thyroid in colloid); made when needed |
| Transport in blood | Mostly free | Mostly bound to carrier proteins |
| Half-life | Short (minutes) | Long (hours to days) |
| Receptor | Cell surface | Intracellular (cytoplasm or nucleus) |
| Mechanism | Second messengers; fast effects | Change gene transcription; slow, lasting effects |
| Given by mouth? | Usually not (digested); insulin is injected | Often yes |
Protein-bound and free hormone
Lipid-soluble hormones travel bound to carriers: thyroxine-binding globulin, cortisol-binding globulin, sex hormone-binding globulin, and albumin.
- Only the free fraction can enter cells and act.
- The bound fraction is a reservoir that keeps levels steady and prolongs half-life.
- Feedback responds to the free level.
In pregnancy or with the oral contraceptive pill, oestrogen raises binding globulins. Total T4 and cortisol rise, but the free levels (and function) stay normal.
Receptors and how they signal
Cell-surface receptors
| Receptor type | Second messenger | Examples |
|---|---|---|
| G protein (Gs) | ↑ cAMP → protein kinase A | Glucagon, ACTH, TSH, LH, FSH, PTH, ADH (V2), β-adrenergic |
| G protein (Gi) | ↓ cAMP | Somatostatin, α2-adrenergic |
| G protein (Gq) | IP3 (Ca2+ release) and DAG (protein kinase C) | ADH (V1), oxytocin, GnRH, TRH, angiotensin II, α1-adrenergic |
| Tyrosine kinase | Receptor phosphorylates itself and other proteins | Insulin, IGF-1, growth factors |
| Cytokine receptor (JAK-STAT) | Associated JAK kinase | Growth hormone, prolactin, erythropoietin |
| Guanylyl cyclase | ↑ cGMP | ANP, nitric oxide |
Intracellular receptors
Steroids and thyroid hormones cross the membrane and bind receptors in the cytoplasm or nucleus. The hormone-receptor complex binds hormone response elements on DNA and switches genes on or off. Effects take hours and last long.
Specificity
A hormone acts only on cells with its receptor. Exceptions arise when hormones are similar and cross-react:
- High cortisol can act on mineralocorticoid receptors (normally protected by an enzyme in the kidney), causing salt retention.
- hCG acts on the LH receptor (and at very high levels on the TSH receptor).
- High ADH can act on oxytocin receptors and vice versa.
Control of secretion
Negative feedback
The usual control. The hormone, or its effect, reduces its own release. Example: cortisol suppresses CRH and ACTH; high blood glucose stops glucagon release.
Positive feedback
Rare. The hormone increases its own release. Examples: the LH surge before ovulation (driven by high oestrogen) and oxytocin during labour.
Rhythms
Many hormones are released in pulses (GnRH) or follow a daily (circadian) rhythm (cortisol highest in the early morning; growth hormone highest in deep sleep).
Hormone activity: modifying factors
- Permissive action: one hormone allows another to work fully. Cortisol is needed for catecholamines to cause vasoconstriction and for glucagon to increase gluconeogenesis; thyroid hormone is needed for growth hormone to work fully and increases β-receptors.
- Down-regulation: long exposure to high hormone levels reduces receptor number (receptors are taken into the cell and destroyed). This causes resistance to the hormone. Example: continuous GnRH (rather than pulses) suppresses LH and FSH.
- Up-regulation: low levels or another hormone increase receptor number.
- Synergism and antagonism between hormones.
Continuous GnRH analogue treatment down-regulates pituitary receptors and suppresses sex hormones, used in prostate cancer and endometriosis.
Disorders of the endocrine system
| Type | Causes | Examples |
|---|---|---|
| Hypofunction | Gland destruction (autoimmune, infection, surgery), lack of stimulating hormone, enzyme defects | Hypothyroidism, Addison's disease, type 1 diabetes |
| Hyperfunction | Tumour, hyperplasia, stimulating antibodies, ectopic hormone | Graves' disease, Cushing's syndrome, phaeochromocytoma |
| Receptor or signalling defects (hormone resistance) | Hormone level normal or high but no response | Type 2 diabetes (insulin resistance), nephrogenic diabetes insipidus, androgen insensitivity |
| Changes in gland size | Hyperplasia or atrophy | Goitre; adrenal atrophy after long steroid treatment |
Primary disease is in the target gland (hormone low, stimulating hormone high). Secondary disease is in the pituitary (both low). Tertiary disease is in the hypothalamus.
Expect: which hormones act on intracellular vs surface receptors, the second messenger for common hormones (cAMP, IP3, tyrosine kinase, JAK-STAT), why only free hormone is active, negative vs positive feedback examples, permissive action of cortisol and thyroid hormone, down-regulation, and primary vs secondary endocrine failure.
Quick revision
- Peptides and catecholamines: surface receptors, second messengers, short half-life.
- Steroids and thyroid hormones: protein-bound, intracellular receptors, gene transcription.
- Only free hormone acts; binding proteins are a reservoir.
- Gs → cAMP; Gq → IP3/DAG; insulin → tyrosine kinase; GH, prolactin → JAK-STAT; ANP → cGMP.
- Negative feedback is the rule; LH surge and oxytocin in labour are positive feedback.
- Permissive: cortisol for catecholamines and glucagon.
- High hormone levels down-regulate receptors.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
Which hormones bind intracellular receptors?
Steroid hormones and thyroid hormones.
Why are steroid hormones longer-acting than peptide hormones?
They are carried bound to plasma proteins, which protects them from breakdown, and they act by changing gene expression.
What is permissive action?
When one hormone must be present for another to have its full effect, such as cortisol allowing catecholamines to constrict blood vessels.
What is down-regulation?
A fall in the number of receptors after long exposure to high hormone levels, reducing the response.