The mechanism. Hormones produce their effects on target tissues by binding to specific proteins called hormone receptors, located in the target tissues only. Binding leads to the formation of a hormone-receptor complex, and this complex formation leads to certain biochemical changes in the target tissue. Moreover, each receptor is specific to one hormone only, so receptors are specific.

The selectivity therefore lies in the receiving tissue, not in the hormone or in its delivery. A tissue lacking the receptor is simply deaf to the message, no matter how much hormone bathes it.

The prediction. If a normally unresponsive tissue were made to express the receptor, it would begin to respond to that hormone: the hormone-receptor complex would form there, biochemical changes would follow, and the tissue's metabolism and physiological function would now be regulated by a hormone that previously did nothing to it.

What the thought experiment establishes: the hormone carries the signal, but the target tissue determines the response. This is the same principle you met at the chemical synapse in Chapter 18, where the post-synaptic neuron's own receptors and ion channels decide whether a neurotransmitter excites or inhibits it.

Testosterone — a steroid. Hormones which interact with intracellular receptors, such as steroid hormones and iodothyronines, mostly regulate gene expression or chromosome function by the interaction of the hormone-receptor complex with the genome. Changing which genes a cell expresses changes what proteins it builds, and therefore what the cell is. Androgens accordingly produce structural, developmental changes: development and maturation of the male accessory sex organs, muscular growth, growth of facial and axillary hair, low pitch of voice. Once the tissue has been rebuilt, the change persists.

Insulin — a peptide. Hormones which interact with membrane-bound receptors normally do not enter the target cell but generate second messengers (cyclic AMP, IP₃, Ca⁺⁺) which in turn regulate cellular metabolism. Insulin therefore alters what the existing cell machinery is doing right now — enhancing cellular glucose uptake and utilisation and stimulating glycogenesis. When the hormone leaves and the second messengers are degraded, the cell reverts to its previous behaviour.

The general rule: hormones that change gene expression produce slow, lasting, developmental effects; hormones that change metabolism through second messengers produce rapid, reversible effects. The body needs both, since glucose must be adjusted many times a day while puberty happens once.

Lowering: the atrial wall of our heart secretes a peptide hormone called atrial natriuretic factor (ANF), which decreases blood pressure. When blood pressure is increased, ANF is secreted, which causes dilation of the blood vessels, and this reduces the blood pressure.

Raising: aldosterone, the main mineralocorticoid of the adrenal cortex, acts mainly at the renal tubules and stimulates reabsorption of Na⁺ and water, thereby helping maintain body fluid volume, osmotic pressure and blood pressure.

Why the heart is a good sensor. The atrial wall is stretched by the very quantity being regulated: when blood pressure and volume rise, the atria are distended. A hormone secreted from that wall is therefore released in direct proportion to the disturbance it must correct, and its effect — vasodilation — removes the cause of its own secretion. This is a self-limiting feedback loop with the sensor and the secretory tissue in the same place, which is faster and more reliable than routing the information through a separate gland.

A wider observation: the same design appears elsewhere in the chapter. The secretion of PTH is regulated by the circulating levels of calcium ions; insulin and glucagon respond to blood glucose. Endocrine control is generally built on the regulated variable feeding back on its own controller.

1. Gastrin. As food enters the stomach, gastrin acts on the gastric glands and stimulates the secretion of hydrochloric acid and pepsinogen — the acid and the protein-digesting precursor needed for gastric digestion.

2. Secretin. When the acidic contents pass into the intestine, secretin acts on the exocrine pancreas and stimulates the secretion of water and bicarbonate ions. The bicarbonate neutralises the acid, which is necessary because pancreatic enzymes cannot work in an acid medium.

3. Cholecystokinin (CCK). This acts on both pancreas and gall bladder and stimulates the secretion of pancreatic enzymes and bile juice respectively. For a fatty meal this is the crucial step: bile emulsifies the fat and pancreatic lipase digests it.

4. Gastric inhibitory peptide (GIP). This inhibits gastric secretion and motility, slowing the stomach so that the intestine is not overloaded while the fat is still being handled.

The logic of the sequence: three hormones switch digestive secretions on, each matched to where the food has reached, and the fourth switches the stomach down so that delivery matches the intestine's capacity to process. Notice also that the endocrine cells doing all this are distributed in the wall of the gastro-intestinal tract itself, not gathered into a gland — they are among the "hormone producing diffused tissues/cells" that the definition of the endocrine system includes.

In the young man. LH stimulates the synthesis and secretion of androgens from the testis, and FSH with androgens regulates spermatogenesis. Losing both means the Leydig cells are no longer stimulated, so the production of androgens, mainly testosterone, falls. Consequently: the development, maturation and functions of the male accessory sex organs (epididymis, vas deferens, seminal vesicles, prostate gland, urethra) are impaired; muscular growth, facial and axillary hair growth and the low pitch of voice are not maintained; spermatogenesis fails, since androgens play a major stimulatory role in it; male sexual behaviour (libido), which androgens influence through the central neural system, is reduced; and the anabolic effects on protein and carbohydrate metabolism are lost.

In the young woman. FSH stimulates the growth and development of the ovarian follicles, and LH induces ovulation of fully mature graafian follicles and maintains the corpus luteum. Losing both means follicles do not grow, so the estrogen normally synthesised and secreted mainly by the growing ovarian follicles is not produced — affecting the growth and activities of female secondary sex organs, female secondary sex characters, mammary gland development and female sexual behaviour. No ovulation occurs, so no corpus luteum forms, so progesterone is not secreted — and progesterone supports pregnancy and stimulates the formation of alveoli and milk secretion in the mammary glands. Fertility is therefore lost in both sexes.

The point of the question: a lesion high in the hierarchy produces failure of every hormone below it. This is why the hypothalamus–pituitary–peripheral gland chain, efficient as it is for coordination, concentrates risk at the top.