Chemical Coordination and Integration: Class 11 Biology · Chapter 19

A dog lunges at you from behind a gate. In a fraction of a second your legs jerk you backwards: nerve impulses, racing along fixed pathways, did that. Yet a full minute later your heart is still pounding, your palms are damp and you feel wide awake, long after the dog has gone quiet. That lingering state is the work of chemicals carried in your blood.

Neural control, which you studied in the previous chapter, is fast and precise but short-lived, and it reaches only the cells that a nerve fibre actually supplies. Many jobs need something else: growth that continues for years, a blood glucose level held steady day and night, a menstrual cycle timed over weeks. For these the body uses hormones (हॉर्मोन), messengers that travel in the blood to almost every cell. The two systems are partners: together the neural system and the endocrine system coordinate and regulate the body's physiology (Fig. 19.1).

19.1 Endocrine glands and hormones

Your body has two kinds of glands. A salivary gland or a sweat gland pours its product into a tube, a duct, which delivers it to one spot such as the mouth or the skin. These are exocrine glands. An endocrine gland (अंतःस्रावी ग्रंथि) has no duct at all. Its cells release their product into the fluid around them, and from there it passes into nearby blood capillaries (Fig. 19.2). Endocrine glands are therefore also called ductless glands, and their secretions are hormones.

The older textbook idea of a hormone was narrow: a chemical made by an endocrine gland, poured into the blood and carried to a distant target organ. It fitted the classic glands. But biologists kept finding messengers that broke the rule: hormones from the heart wall, the gut lining and the kidney, none of which is a gland, and signals that act on cells close to where they are made. So the definition now describes what a hormone does, not where it comes from.

• Non-nutrient: a hormone is information, not food or fuel. Glucose in blood is a nutrient; insulin, which controls it, is not.
• A messenger between cells: it carries a signal from the cell that makes it to a cell that responds.
• Trace amounts: tiny concentrations are enough, as Example 19.1 shows.

Simple animals manage with a small set of hormones; an insect, for example, relies on just a few to control moulting and metamorphosis. Vertebrates use a large array of hormones to coordinate their many organ systems. The rest of this chapter is about the human endocrine system.

19.2 Human endocrine system

Your endocrine system has two parts. One is a set of separate, organised glands: the pituitary, pineal, thyroid, parathyroid, thymus, adrenal, pancreas and the gonads (testes in males, ovaries in females). The other is hormone-making tissue tucked inside organs whose main job lies elsewhere, such as the gastrointestinal tract, liver, kidney and heart. The hypothalamus, a part of the brain, directs much of the system. Fig. 19.3 shows where each gland sits, and Table 19.1 lists their hormones.

19.2.1 The hypothalamus

You met the hypothalamus in the previous chapter as a centre for body temperature, hunger and thirst. It sits at the base of the diencephalon, in the forebrain, and it is also a hormone factory. Clusters of its neurons, the neurosecretory cells or nuclei, secrete hormones. Nearly all of these are aimed at one gland, the pituitary, and they carry one of two instructions: releasing hormones tell the pituitary to secrete, and inhibiting hormones tell it to hold back.

Gonadotrophin releasing hormone (GnRH), for instance, makes the pituitary produce and release the hormones that drive the testes and ovaries. Somatostatin, also from the hypothalamus, works the other way: it damps down the pituitary's release of growth hormone.

How do these hormones reach the pituitary just below? Follow the two routes in Fig. 19.4. In the first, releasing and inhibiting hormones flow down the axons of hypothalamic neurons and leave at their nerve endings. There they enter a short portal circulation, vessels that carry blood from one capillary bed directly to a second capillary bed in the anterior pituitary without first going round the body, so the hormones arrive concentrated. The posterior pituitary is wired differently: hypothalamic neurons send their axons right into it, so it is under direct neural control.

19.2.2 The pituitary gland

The pituitary (पीयूष ग्रंथि) is about the size of a pea. It hangs from the hypothalamus by a stalk and rests in a bony hollow of the skull floor called the sella turcica, Latin for 'Turkish saddle', which describes its shape. The gland has two parts that work very differently:

• the adenohypophysis, the glandular part, made of the pars distalis (the anterior pituitary) and a thin pars intermedia, which in humans has almost merged with the pars distalis;
• the neurohypophysis, or pars nervosa (the posterior pituitary), which is really an outgrowth of the hypothalamus and makes no hormones of its own.

The pars distalis secretes six hormones, usually known by their abbreviations: TSH (thyroid stimulating hormone), ACTH (adrenocorticotrophic hormone), GH (growth hormone), PRL (prolactin), FSH (follicle stimulating hormone) and LH (luteinizing hormone). The pars intermedia secretes a single hormone, MSH (melanocyte stimulating hormone). The neurohypophysis stores and releases oxytocin and vasopressin, which are synthesised by hypothalamic neurons and sent down their axons. Table 19.2 and Fig. 19.5 pair each hormone with its target.

Growth hormone shows how the timing of an imbalance shapes its effect. Before puberty the long bones can still lengthen; in an adult they cannot, but bone and soft tissue can still thicken.

Prolactin builds up the mammary glands and drives milk production in them. TSH and ACTH are trophic hormones, each switching on another endocrine gland: TSH acts on the thyroid, so that it makes and releases its hormones, and ACTH on the adrenal cortex, so that it makes and releases the steroids called glucocorticoids. Because their targets are the gonads, LH and FSH are grouped together as gonadotrophins.

In a male, LH is the signal for the testes to produce androgens, while sperm production (spermatogenesis) needs FSH working together with those androgens. In a female, FSH drives the growth and development of the ovarian follicles. LH then causes a fully mature (Graafian) follicle to release its ovum, which is ovulation, and afterwards sustains the corpus luteum that the emptied follicle turns into.

Skin colour is the business of MSH, which acts on melanocytes, the skin's melanin-containing cells. Oxytocin is a signal to smooth muscle to contract, seen most dramatically in the strong uterine contractions of childbirth and in the ejection of milk from the mammary glands while a baby feeds. Vasopressin works mainly on the kidney: in the distal tubules it increases the reabsorption of water and electrolytes, so less water is lost as urine. A heavy flow of urine is called diuresis, so vasopressin is also named antidiuretic hormone (ADH).

When the body fails to make or release enough ADH, urine stays dilute and plentiful however little the person drinks, and constant thirst and dehydration follow. This condition is diabetes insipidus.

19.2.3 The pineal gland

The pineal gland is a tiny body on the dorsal side of the forebrain, and its hormone, melatonin, works as the body's clock for the 24-hour, or diurnal, cycle. It makes you sleepy at night and helps your body temperature dip and rise on a daily schedule. Its reach goes further: metabolism, skin pigmentation, the menstrual cycle and the body's immune defences all respond to it.

Melatonin output follows light and darkness (Fig. 19.6). Through the day it stays low; after dusk it climbs, peaks in the small hours of the night and falls again towards morning.

19.2.4 The thyroid gland

Touch your neck just below the Adam's apple and swallow: the thyroid lies there, against the front of the trachea. It has two lobes, one on either side of the trachea, joined across the front by a thin band of connective tissue called the isthmus (Fig. 19.7). Inside, the gland is built of many hollow, ball-shaped follicles held in stromal (supporting) tissue. The wall of each follicle is a ring of follicular cells around a central cavity filled with a protein-rich colloid.

The follicular cells make two hormones: tetraiodothyronine, better known as thyroxine (${\mathrm{T}}_4$), and triiodothyronine (${\mathrm{T}}_3$). The prefixes count iodine atoms, four in one molecule and three in the other. That is why the thyroid cannot keep up its normal rate of hormone synthesis unless the diet supplies enough iodine.

Thyroid hormones act on almost every tissue, like an accelerator for the body's chemistry. They set the basal metabolic rate, the energy used at rest, and with it how fast carbohydrates, proteins and fats are processed. The nervous system needs them in order to develop and mature; they also influence the balance of water and electrolytes and support red blood cell formation. Separately, the thyroid secretes a protein hormone, thyrocalcitonin (TCT), that helps keep blood calcium in check (Section 19.2.5).

19.2.5 The parathyroid glands

Turn the thyroid round and four small parathyroid glands come into view on its back, two on each lobe (last step of Fig. 19.7). Their peptide hormone is parathyroid hormone (PTH). No other gland switches them on: the parathyroid cells themselves sense the calcium ions ($\mathrm{C}\mathrm{a}{\phantom{X}}^{2+}$) in the blood flowing past and adjust their output. PTH raises blood calcium by acting in three places:

• Bone: it stimulates bone resorption, the dissolving (demineralisation) of bone mineral, which frees $\mathrm{C}\mathrm{a}{\phantom{X}}^{2+}$ into the blood.
• Kidney: it makes the renal tubules reabsorb more $\mathrm{C}\mathrm{a}{\phantom{X}}^{2+}$, so less is lost in urine.
• Intestine: it increases the absorption of $\mathrm{C}\mathrm{a}{\phantom{X}}^{2+}$ from digested food.

All three actions push blood calcium up, so PTH is a hypercalcemic hormone. Thyrocalcitonin pushes the other way and lowers it. Like two hands on a steering wheel, PTH and TCT hold blood calcium within a narrow range (Fig. 19.8), which matters because nerves, muscles (the heart included) and blood clotting all depend on calcium.

19.2.6 The thymus

Behind your breastbone (sternum), tucked between the two lungs on the ventral side of the aorta, lies a soft, lobed gland: the thymus. Think of it as a training school for the immune system. The peptide hormones it releases, the thymosins, guide young T-lymphocytes as they differentiate into the cells responsible for cell-mediated immunity, and they boost antibody production, the basis of humoral immunity.

This school shrinks with age. In elderly people the thymus has largely degenerated and makes little thymosin, so their immune defences are weaker; that is one reason an infection a teenager shrugs off can be dangerous for a grandparent. You will meet T-cells and antibodies again in Class 12, in the chapter on human health and disease.

19.2.7 The adrenal glands

You have two adrenal glands (अधिवृक्क ग्रंथि), each sitting like a cap on top of a kidney. Slice one open and you see two different tissues: a central adrenal medulla wrapped in an outer adrenal cortex (Fig. 19.9). The two make entirely different hormones, so it helps to think of them as two glands in one package.

The medulla: emergency hormones. In any kind of stress or emergency the medulla rapidly pours out adrenaline (epinephrine) and noradrenaline (norepinephrine), grouped as catecholamines. Because they ready the body to fight or to run, they are nicknamed the emergency hormones, or the 'fight or flight' hormones. Think back to the dog at the gate:

• your heart speeds up and each beat is more forceful, and your breathing quickens;
• fuel is mobilised: glycogen is broken down so blood glucose rises, and lipids and proteins are broken down too;
• you feel alert, your pupils widen (pupillary dilation), you sweat, and the hairs on your skin stand on end (piloerection).

The cortex: three zones, many corticoids. From the outside in, the cortex is layered into the zona glomerulosa, the zona fasciculata and the zona reticularis. Together they release several steroid hormones, the corticoids, of two main families. Glucocorticoids, led in humans by cortisol, deal with carbohydrate metabolism. Mineralocorticoids, led by aldosterone, manage the body's water and electrolytes.

Doctors prescribe synthetic glucocorticoids for severe allergies and inflammation, and the reason lies in what cortisol does naturally: it damps inflammation and suppresses the immune response. Its metabolic effects are broad. It drives gluconeogenesis (new glucose from non-carbohydrate sources), lipolysis (fat breakdown) and proteolysis (protein breakdown) while holding back the uptake and use of amino acids by cells. It also helps to maintain the cardiovascular system and kidney function, and it stimulates red blood cell production.

Aldosterone acts mainly on the renal tubules. It increases the reabsorption of $\mathrm{N}\mathrm{a}{\phantom{X}}^{+}$ and water and the excretion of $\mathrm{K}{\phantom{X}}^{+}$ and phosphate ions, and so it keeps blood pressure, the volume of body fluids, their osmotic pressure and the electrolyte balance steady.

The cortex also releases small amounts of androgenic steroids, which help hair grow in the armpits, on the pubic region and on the face during puberty. If the cortex makes too little hormone, carbohydrate metabolism is disturbed and the person suffers acute weakness and fatigue: this is Addison's disease.

19.2.8 The pancreas

The pancreas (अग्न्याशय) is a composite gland, exocrine and endocrine at once. Most of it makes pancreatic juice that flows through a duct into the duodenum. Scattered through it like islands are about 1 to 2 million small clusters of endocrine cells, the islets of Langerhans, yet together they amount to just 1–2 % of the gland's tissue. The two main kinds of islet cell are the $\alpha$-cells, which secrete glucagon, and the $\beta$-cells, which secrete insulin.

Between meals it is glucagon that stops your blood sugar from sagging. This peptide hormone works mainly on liver cells (hepatocytes) and makes them release glucose in two ways: by breaking down stored glycogen (glycogenolysis) and by building new glucose from non-carbohydrate sources (gluconeogenesis). At the same time it makes body cells take up and use less glucose. Every one of these effects pushes blood sugar up, towards hyperglycemia, which is why glucagon is called a hyperglycemic hormone.

After a meal the job passes to insulin, also a peptide. Its main targets are hepatocytes and adipocytes (fat cells), which it makes take in and use glucose faster; it also has them lock surplus glucose away as glycogen (glycogenesis). Glucose streams out of the blood and the level falls, and if it drops below normal the state is hypoglycemia. With glucagon raising and insulin lowering it, blood glucose stays steady: glucose homeostasis ((19.1), Fig. 19.10).

If insulin is missing, or the body's cells stop responding to it, blood glucose stays high day after day. This long-lasting hyperglycemia is the complex disorder diabetes mellitus (मधुमेह).11An ICMR study published in 2023 estimated that about 101 million people in India live with diabetes. The kidneys cannot reclaim all the extra glucose, so some is lost in urine; and cells unable to use glucose properly turn to fat for energy, forming harmful ketone bodies. Insulin therapy controls the disease well, and people whose pancreas makes no insulin depend on it.

19.2.9 Testis

The testes (वृषण) hang in the scrotal sac, outside the abdomen, and lead a double life: as the primary male sex organs they make sperms, and as endocrine glands they make hormones. Most of each testis is coiled seminiferous tubules, where sperms form. The hormone makers are the Leydig cells (interstitial cells), scattered in the stromal, or interstitial, tissue that fills the spaces between the tubules. They secrete the androgens, of which testosterone is the chief (Fig. 19.12).

• Sperm production: androgens are a major stimulus for spermatogenesis.
• Puberty: they build muscle and bring facial and axillary (armpit) hair, a deeper (low-pitched) voice and aggressiveness.
• Accessory organs: the epididymis, vas deferens, seminal vesicles, prostate gland and urethra need androgens to develop, mature and work.
• Metabolism: they have anabolic (building-up) effects on protein and carbohydrate metabolism and stimulate red blood cell formation.
• Behaviour: acting on the central nervous system, they influence male sexual behaviour (libido).

19.2.10 Ovary

The two ovaries (अंडाशय), inside the female abdomen, also have two roles. In each menstrual cycle one ovum is released, and the ovaries secrete steroid hormones of two groups, estrogen and progesterone. Which hormone dominates depends on what the ovarian follicles, set in a supporting stroma, are doing (last three steps of Fig. 19.12). A growing follicle secretes mainly estrogen. Once it has released its ovum, the ruptured follicle becomes the corpus luteum, whose main product is progesterone.

At puberty, estrogens bring on the female secondary sex characters, such as a high-pitched voice, and develop the mammary glands. Throughout reproductive life they stimulate the growth and activity of the female secondary sex organs, help growing follicles develop and regulate female sexual behaviour. Progesterone's chief task is to support pregnancy; in the mammary glands it builds alveoli, the sac-like structures that store milk, and stimulates milk secretion. Class 12 shows how these hormones work with LH and FSH to run the menstrual cycle.

19.3 Hormones of heart, kidney and gastrointestinal tract

Not every hormone comes from a gland. Several organs whose main work lies elsewhere also contain hormone-secreting cells (Fig. 19.13, Table 19.6).

Even the heart is an endocrine organ. Its atrial walls release a peptide, atrial natriuretic factor (ANF), whenever blood pressure climbs. ANF widens (dilates) the blood vessels, and wider vessels mean lower pressure, so ANF acts as a built-in brake on blood pressure.22Natriuretic means 'promoting the loss of sodium in urine', another effect of ANF on the kidney.

In the kidney, the juxtaglomerular cells release erythropoietin, a peptide hormone that tells the bone marrow to step up erythropoiesis, the making of red blood cells. People whose kidneys fail make too little of it and often become anaemic; they can be treated with erythropoietin made by recombinant DNA technology.

Endocrine cells scattered along the gastrointestinal tract release four major peptide hormones, each matched to a stage of digestion. Gastrin makes the gastric glands pour out hydrochloric acid and pepsinogen. Secretin targets the exocrine pancreas, which answers with a flow of water and bicarbonate ions. Cholecystokinin (CCK) has two targets: the pancreas, which releases its enzymes, and the gall bladder, which releases bile juice. Gastric inhibitory peptide (GIP) holds back both gastric secretion and the churning movements (motility) of the stomach.

Beyond these, many non-endocrine tissues release growth factors. Tissues need these signals to grow normally and to repair or regenerate themselves after injury.

19.4 Mechanism of hormone action

Glucagon reaches every cell in the body, yet liver cells respond strongly and skin cells hardly at all. The difference lies in hormone receptors (ग्राही), proteins that recognise and bind one particular hormone and are present only in its target tissues. Each receptor binds only its own hormone, so receptors are specific. Binding forms a hormone–receptor complex, and the complex sets off biochemical changes that alter the target tissue's metabolism and, through it, its physiological functions.

Receptors sit in one of two places. Membrane-bound receptors lie in the cell membrane of the target cell. Intracellular receptors lie inside it, mostly in the nucleus, where they are called nuclear receptors. Which kind a hormone uses depends largely on its chemical nature (Table 19.7).

Peptide hormones and adrenaline cannot cross the membrane, so they deliver their message at the surface by binding membrane-bound receptors. Binding changes the receptor, which then sets off the production of a second messenger inside the cell: cyclic AMP (cAMP), inositol trisphosphate ($\mathrm{I}{\mathrm{P}}_3$) or calcium ions ($\mathrm{C}\mathrm{a}{\phantom{X}}^{2+}$), for example. If the hormone is the first messenger, delivering the signal to the cell surface, the second messenger carries it on inside, switching enzymes on or off and so regulating cellular metabolism. When glucagon binds a liver cell, cAMP rises and the enzymes that break down glycogen are activated (Fig. 19.14).

Steroids and iodothyronines take the other route. Steroids are lipid-soluble and pass straight through the membrane, and these hormones find their receptors inside the cell, mostly in the nucleus. There the hormone–receptor complex works on the genome itself, switching particular genes on or off (gene expression) or otherwise affecting chromosome function, so the cell starts making a different set of proteins. Added up over time, these biochemical changes show as physiological and developmental effects.