How One Hormone Molecule Can Switch On a Whole Cell

A hormone travelling in blood passes countless cells, yet changes only a few. Its effect depends on the receptor it meets and on how much of it is present — too little or too much can cause disease.

This part covers hormones from non-endocrine tissues, how hormones act, growth and thyroid disorders, and diabetes mellitus and Addison's disease.

The atrial wall of the heart releases atrial natriuretic factor, which lowers blood pressure; juxtaglomerular cells of the kidney release erythropoietin, which stimulates red blood cell formation; and the gut releases gastrin, secretin, cholecystokinin and gastric inhibitory peptide, which coordinate digestion.

Heart:

- Atrial natriuretic factor (ANF) — a peptide from the atrial wall
- Released when blood pressure rises; it dilates blood vessels, lowering blood pressure

Kidney:

- Erythropoietin — from juxtaglomerular cells
- Stimulates erythropoiesis, the formation of RBCs

Gastrointestinal tract — endocrine cells secrete four major peptide hormones:

- Gastrin — acts on gastric glands, stimulating hydrochloric acid and pepsinogen secretion
- Secretin — acts on the exocrine pancreas, stimulating secretion of water and bicarbonate ions
- Cholecystokinin (CCK) — acts on the pancreas and gall bladder, stimulating pancreatic enzymes and bile
- Gastric inhibitory peptide (GIP) — inhibits gastric secretion and motility

An everyday example. After a rich meal of puri and bhaji, cholecystokinin signals the gall bladder to release bile to help digest the fat.

The substance. Hormone-secreting tissue need not be a gland — the heart and gut are organs with other main jobs.

**Protein and peptide hormones cannot enter cells, so they bind membrane receptors and trigger second messengers such as cyclic AMP and Ca${}^{2+}$ that change cell metabolism, while lipid-soluble steroid and thyroid hormones enter the cell, bind intracellular receptors, and regulate gene expression.

Hormone receptors. Hormones act by binding specific receptors found only in target tissues, forming a hormone-receptor complex that triggers biochemical changes.

Membrane-bound receptors:

- Used by hormones that do not enter the cell — peptide and protein hormones such as insulin, glucagon and pituitary and hypothalamic hormones, and amino-acid derivatives such as adrenaline
- Binding generates second messengers, such as cyclic AMP, IP${}_3$ and Ca${}^{2+}$
- The second messengers regulate cellular metabolism

Intracellular receptors:

- Used by hormones that cross the membrane — steroid hormones such as cortisol, testosterone, oestradiol and progesterone, and iodothyronines (thyroid hormones)
- Mostly nuclear receptors; the hormone-receptor complex interacts with the genome
- They regulate gene expression or chromosome function, producing physiological and developmental effects

An everyday example. A doorbell that switches on lights throughout a house is like a membrane receptor: the visitor never enters, but a signal inside spreads the message.

The substance. Second-messenger effects are usually quick, while gene-level steroid effects take longer**, because new proteins must be made.

Too little growth hormone in childhood causes dwarfism and too much causes gigantism, while excess in adults causes acromegaly; too little thyroid hormone during development causes cretinism, iodine deficiency causes goitre, and too much thyroid hormone causes hyperthyroidism, including exophthalmic goitre.

Growth hormone:

- Over-secretion in childhood — gigantism, abnormally tall growth
- Low secretion in childhood — pituitary dwarfism, stunted growth
- Excess in adults, especially in middle age — acromegaly, with severe disfigurement, especially of the face; it can go unnoticed for years

Thyroid hormones:

- Iodine deficiency — hypothyroidism and an enlarged thyroid, goitre
- Hypothyroidism during pregnancy — defective development of the baby, causing cretinism: stunted growth, impaired mental development, abnormal skin and deaf-mutism
- Hyperthyroidism — abnormally high thyroid hormone levels, for example from thyroid nodules, harming normal body physiology
- Exophthalmic goitre (Graves' disease) — a form of hyperthyroidism with an enlarged thyroid, protruding eyeballs, higher basal metabolic rate and weight loss

An everyday example. A neck swelling noticed at a health camp may lead a doctor to test thyroid hormone levels.

The substance. Goitre can occur with too little or too much thyroid hormone — the swelling alone does not tell which.

Diabetes mellitus results from too little insulin or a poor response to it, causing high blood glucose, glucose in urine and harmful ketone bodies, and is managed with insulin and lifestyle care; Addison's disease results from too little hormone secretion by the adrenal cortex, causing weakness and fatigue, and is managed with hormone replacement.

Diabetes mellitus:

- Cause — prolonged hyperglycaemia due to deficient insulin action
- Signs — loss of glucose through urine and formation of harmful ketone bodies
- Management — insulin therapy, with diet control and exercise
- Insulin lowers blood glucose by increasing glucose uptake into cells and promoting glycogen formation

Addison's disease:

- Cause — under-secretion of hormones by the adrenal cortex, including cortisol and aldosterone
- Effects — altered carbohydrate metabolism causing acute weakness and fatigue; loss of Na${}^{+}$ and water can lower blood pressure
- Management — lifelong replacement of adrenal cortical hormones under medical care

Worked example — read a test. A very thirsty person passing large volumes of urine has glucose and ketone bodies in the urine: the likely condition is diabetes mellitus.

An everyday example. People with diabetes checking their blood sugar with a small finger-prick meter are monitoring how well treatment keeps glucose in range.

The substance. Diabetes mellitus and diabetes insipidus share a name but not a cause — one involves insulin and sugar, the other ADH and water.