In 1921 a child diagnosed with type 1 diabetes in Canada was expected to die within months, often on a starvation diet. By 1923, children who had been near death were eating normally and growing again, thanks to a hormone extracted at the University of Toronto: insulin. A hormone is a chemical messenger released into the blood in tiny amounts that changes the behaviour of distant cells. The nervous system is like a phone call, fast and sent to one specific cell. The endocrine system is more like a radio broadcast: the message goes everywhere in the blood, but only cells with the right receptor tune in, and the effects can last hours, days or years. Endocrine glands are ductless: they secrete hormones directly into the blood. (Exocrine glands, such as sweat and salivary glands, release their products through ducts.) A target cell is any cell with a receptor protein that fits a particular hormone. A hormone can reach every cell in the body, yet affect only its targets. How it acts depends on whether it can cross the cell membrane.
- Made from cholesterol; lipid-soluble
- Diffuse straight through the phospholipid bilayer
- Bind a receptor inside the cell (cytoplasm or nucleus)
- Hormone–receptor complex binds DNA and changes gene expression (turns transcription on or off)
- Slower to act (hours) but long-lasting
- Examples: cortisol, aldosterone, testosterone, estrogen, progesterone (thyroxine is not a steroid but acts the same way)
- Chains of amino acids (or amino-acid derivatives); water-soluble
- Cannot cross the bilayer
- Bind a receptor on the cell membrane
- Receptor activates a second messenger inside the cell, such as cAMP, which triggers an enzyme cascade
- Fast (seconds to minutes); the cascade amplifies the signal
- Cascade: hormone binds receptor → G protein → adenylyl cyclase converts ATP to cAMP → protein kinases switch on enzymes (e.g. glycogen breakdown in liver). Each step activates many molecules of the next, so one hormone molecule can yield millions of product molecules without ever entering the cell
- Examples: insulin, glucagon, ADH, oxytocin, FSH, LH, TSH, GH (adrenaline, an amine, acts the same way)
The hypothalamus links the nervous and endocrine systems. It sits just above the pituitary gland, a pea-sized gland once called the "master gland" because many of its hormones control other glands. The pituitary has two parts that work very differently. The anterior pituitary is true glandular tissue: the hypothalamus sends it releasing hormones through a small network of blood vessels (the portal system), and in response the anterior pituitary makes and secretes its own hormones. The posterior pituitary is really an extension of the brain: neurons whose cell bodies are in the hypothalamus make ADH and oxytocin, carry them down their axons and store them in the posterior pituitary until a nerve signal releases them. The thyroid shows how hormone levels are held steady by negative feedback. When metabolic rate or thyroxine level is low, the hypothalamus releases TRH (thyrotropin-releasing hormone), which makes the anterior pituitary release TSH, which makes the thyroid release thyroxine (T₄, with some T₃). Thyroxine raises the metabolic rate of nearly every cell. As thyroxine rises, it inhibits both the hypothalamus and the pituitary, so TRH and TSH fall. Thyroxine contains iodine. With too little iodine in the diet, the thyroid cannot make enough thyroxine, so there is no negative feedback; TSH stays high and keeps stimulating the thyroid, which enlarges into a goitre. Canada requires table salt to be iodized, which is why iodine-deficiency goitre is now rare here.
| Hormone | Source | Target | Main effect |
|---|---|---|---|
| TSH (thyroid-stimulating hormone) | Anterior pituitary | Thyroid | Stimulates release of thyroxine |
| ACTH (adrenocorticotropic hormone) | Anterior pituitary | Adrenal cortex | Stimulates release of cortisol |
| FSH (follicle-stimulating hormone) | Anterior pituitary | Ovaries / testes | Follicle development / sperm production |
| LH (luteinizing hormone) | Anterior pituitary | Ovaries / testes | Ovulation and corpus luteum / testosterone production |
| GH (growth hormone) | Anterior pituitary | Most cells, bone, muscle | Growth, protein synthesis, fat breakdown |
| Prolactin | Anterior pituitary | Mammary glands | Milk production |
| ADH (antidiuretic hormone) | Made in hypothalamus, released by posterior pituitary | Kidney collecting ducts | Increases water reabsorption |
| Oxytocin | Made in hypothalamus, released by posterior pituitary | Uterus, mammary glands | Uterine contractions in labour; milk ejection |
Blood glucose and the stress response
Blood glucose is normally held at about 4–7 mmol/L. The receptor and the control centre are the same organ: small clusters of endocrine cells in the pancreas called the islets of Langerhans. When glucose rises after a meal, beta cells secrete insulin. Insulin makes muscle and fat cells insert more glucose transporters into their membranes and take up glucose, and makes the liver and muscles convert glucose into glycogen for storage. When glucose falls, between meals or during exercise, alpha cells secrete glucagon, which makes the liver break glycogen back into glucose and make new glucose from amino acids, releasing it into the blood. Insulin and glucagon are antagonistic hormones: their opposite effects give fine control, like having both a heater and an air conditioner. When insulin is missing or ignored (diabetes mellitus, below), glucose stays high in the blood; once it exceeds what the kidneys can reabsorb, glucose appears in the urine and drags water with it by osmosis, causing frequent urination and thirst. Over years, high blood glucose damages blood vessels in the eyes, kidneys, nerves and heart.
- Autoimmune: the immune system destroys the beta cells
- Little or no insulin is made
- Usually begins in childhood or adolescence
- About 5–10% of cases
- Treated with insulin by injection or pump; not preventable
- Target cells respond poorly to insulin (insulin resistance); insulin output may later fall
- Insulin is made, but it does not work well
- Usually begins in adulthood, though increasingly seen in youth
- About 90% of cases
- Risk rises with inactivity, excess body fat, age and family history; managed with diet, exercise, medication and sometimes insulin
| Adrenal stress response | Short-term stress | Long-term stress |
|---|---|---|
| Pathway | Hypothalamus → sympathetic nerves → adrenal medulla (inner part) | Hypothalamus → CRH → anterior pituitary → ACTH → adrenal cortex (outer part) |
| Hormones | Epinephrine (adrenaline) and norepinephrine | Cortisol (a glucocorticoid); the cortex also makes aldosterone (a mineralocorticoid) |
| Speed | Seconds | Minutes to hours; lasts much longer |
| Effects | Heart rate, blood pressure and breathing rate rise; liver releases glucose; blood diverted to muscles and brain; pupils dilate | Cortisol raises blood glucose by making glucose from proteins and fats, and suppresses inflammation and the immune system. Aldosterone makes the kidneys reabsorb Na⁺ (water follows), raising blood volume and pressure. |
Reproductive hormones and the menstrual cycle
Reproduction is controlled by the same kind of hypothalamus–pituitary axis. The hypothalamus releases GnRH (gonadotropin-releasing hormone), which makes the anterior pituitary release FSH and LH. In males, LH stimulates interstitial cells in the testes to make testosterone, and FSH together with testosterone stimulates sperm production. Testosterone drives male secondary sex characteristics (facial hair, deeper voice, muscle growth) and, by negative feedback, inhibits GnRH and LH, so its level stays roughly constant. In females, hormone levels follow a cycle of about 28 days (normally anywhere from about 21 to 35) coordinated by estrogen and progesterone from the ovaries.
| Phase (typical 28-day cycle) | What happens | Feedback |
|---|---|---|
| Menstruation (days 1–5) | The endometrium (uterine lining) is shed because progesterone has fallen | Low estrogen and progesterone remove inhibition, so FSH starts to rise |
| Follicular phase (days 1–13) | FSH stimulates a follicle in the ovary to mature; the follicle secretes increasing estrogen, which rebuilds the endometrium | Low to moderate estrogen inhibits FSH and LH (negative feedback) |
| Ovulation (about day 14) | The LH surge causes the mature follicle to release its egg | High, sustained estrogen switches to positive feedback on the hypothalamus and pituitary, causing a surge of LH (and FSH) |
| Luteal phase (days 15–28) | LH turns the empty follicle into the corpus luteum, which secretes progesterone and estrogen; progesterone thickens and maintains the endometrium | Progesterone and estrogen together inhibit GnRH, FSH and LH, so no new follicle develops |
| No pregnancy | The corpus luteum breaks down after about 10–14 days; progesterone and estrogen fall; the endometrium is shed | Removal of inhibition lets FSH rise, starting a new cycle |
| Pregnancy | The embryo secretes hCG, which keeps the corpus luteum alive so progesterone stays high and the lining is kept | Pregnancy tests detect hCG in urine |
- Hormonal contraception manipulates feedback. Combined birth control pills contain a synthetic estrogen and a synthetic progesterone (a progestin). Taken daily, they keep these hormones steadily high, mimicking the luteal phase: negative feedback suppresses GnRH, FSH and LH, so no follicle matures, there is no LH surge and no ovulation. Progestins also thicken cervical mucus. In the hormone-free days, levels drop and the lining is shed as a withdrawal bleed.
- Anabolic steroids are synthetic relatives of testosterone that increase protein synthesis and muscle mass. Because they act like testosterone, negative feedback shuts down GnRH, LH and FSH, so in males the testes shrink and sperm production falls, and breast tissue can develop (some of the drug is converted to estrogen). Females can develop a deeper voice, facial hair and irregular cycles. Other risks include acne, liver damage, harmful blood cholesterol changes, heart disease, aggression and, in teens, early closing of the growth plates in bones, which permanently limits height. Canadian sprinter Ben Johnson lost his 1988 Olympic gold medal after testing positive for the steroid stanozolol.
- Endocrine disruptors are chemicals in the environment that mimic, block or interfere with hormones. Synthetic estrogen (ethinylestradiol, from birth control pills) passes through people and wastewater treatment into rivers and lakes. In a whole-lake experiment at the Experimental Lakes Area in northwestern Ontario, adding it at just a few nanograms per litre feminized male fathead minnows and caused the lake's minnow population to collapse. BPA (bisphenol A), used in some hard plastics and can linings, weakly mimics estrogen and leaches out more when plastic is heated or scratched; Canada was one of the first countries to ban it from baby bottles.
- Thyroid treatment: hypothyroidism is treated with synthetic thyroxine (levothyroxine), with the dose adjusted using blood TSH tests, because TSH reflects whether the feedback loop is satisfied. Hyperthyroidism can be treated with radioactive iodine, which the thyroid takes up because it absorbs iodine; the radiation destroys overactive tissue, and the patient often then needs lifelong thyroxine replacement.
- Corticosteroid medications (such as prednisone, a cortisol-like drug for inflammation) suppress CRH and ACTH by negative feedback. With long-term use the adrenal cortex shrinks, so the drug must be tapered off gradually to give the body's own axis time to recover.
- Chemotherapy kills rapidly dividing cells, including cancer cells but also bone marrow, hair follicles and the gut lining. This can cause low white blood cell counts (infection risk), vomiting and diarrhea that disturb water, salt and pH balance, and in some cases kidney damage, so patients' blood chemistry is monitored closely during treatment.