Chemical Coordination and Integration

You have just studied, in the previous chapter, how the nervous system coordinates the body. Nerves are fast and precise, but they have two limits that NCERT states plainly in the opening lines of this chapter. First, the neural system does not reach every cell of the body: nerve fibres innervate muscles, glands and organs, but a hepatocyte deep inside the liver or a bone cell inside its matrix has no nerve ending sitting on it. Second, cellular functions need to be regulated continuously, for hours and days, and a nerve impulse is a momentary event. So the body has a second, slower, chemical system that works through the blood. The endocrine system provides this chemical coordination, and the two systems together, neural and endocrine, coordinate and integrate the physiological functions of the body. That sentence is the answer to the 1-mark question 'why do we need chemical coordination in addition to neural coordination'.

The chapter is organised in four parts and you should keep the map in your head while revising. Part one defines endocrine glands and hormones. Part two, the bulk of the chapter, walks through the human endocrine system gland by gland: hypothalamus, pituitary, pineal, thyroid, parathyroid, thymus, adrenal, pancreas, testis and ovary. Part three lists hormones made by organs that are not primarily endocrine, the heart, kidney and gastrointestinal tract. Part four explains the mechanism of hormone action, the only part of the chapter that asks you to understand a process rather than remember a list. Examiners take 1-mark and 2-mark questions from parts one to three, and the diagram-based 5-mark questions from the pituitary, the adrenal and part four.

Glands are of two kinds. An exocrine gland has a duct and pours its secretion through it onto a surface or into a cavity: salivary glands, sweat glands, the gastric glands and the exocrine part of the pancreas are examples. An endocrine gland lacks ducts, which is why NCERT calls endocrine glands ductless glands; its secretions, the hormones, are released directly into the blood and carried to distant target organs. The classical definition of a hormone was 'a chemical produced by an endocrine gland and released into the blood'. The current NCERT definition is broader and you should reproduce it word for word: hormones are non-nutrient chemicals which act as intercellular messengers and are produced in trace amounts. The three phrases are the three marking points. 'Non-nutrient' separates hormones from glucose and amino acids that also travel in blood. 'Intercellular messengers' says they carry information from one cell to another. 'Trace amounts' says they work at very low concentration, which is why a small deficiency or excess produces a disease.

Why did the definition change? Because it is now known that many organs that are not endocrine glands also make hormones. The gastrointestinal tract, the liver, the kidney and the heart all produce hormones (gastrin, erythropoietin, atrial natriuretic factor), and so do non-endocrine tissues in the form of growth factors. The new definition covers all of these. Together, the endocrine glands and the hormone-producing diffused tissues and cells located in different parts of the body constitute the endocrine system.

The organised endocrine glands of the human body, in the order NCERT lists them, are the pituitary, pineal, thyroid, parathyroid, adrenal, pancreas and the gonads (testis in males, ovary in females). The hypothalamus, though it is a part of the brain, is included because it makes hormones; and the thymus is included with the glands. Learn the locations from NCERT Fig. 19.1, because the exercise asks you to indicate them on a diagram: the pineal at the top of the brain stem on the dorsal side of the forebrain, the hypothalamus and pituitary at the base of the brain, the thyroid and parathyroids in the neck, the thymus behind the sternum, the adrenals on top of each kidney, the pancreas below the stomach, and the gonads in the scrotum or the pelvis.

The hypothalamus is the basal part of the diencephalon, the forebrain. Apart from regulating body temperature, hunger, thirst and other functions studied in the neural chapter, it is the master of the endocrine system, because it controls the pituitary, which in turn controls most of the other glands. That is why the pituitary is called the master gland and the hypothalamus the super master gland or supreme commander.

The hypothalamus contains several groups of neurosecretory cells called nuclei. These are neurons that behave like gland cells: they produce hormones. The hormones are of two kinds. Releasing hormones stimulate the secretion of pituitary hormones, and inhibiting hormones inhibit it. NCERT gives one example of each and both are asked. The gonadotrophin releasing hormone (GnRH) stimulates the pituitary to synthesise and release gonadotrophins (LH and FSH). Somatostatin inhibits the release of growth hormone from the pituitary. Other hypothalamic hormones you meet in the exemplar are thyrotrophin releasing hormone (TRH), corticotrophin releasing hormone (CRH), growth hormone releasing hormone (GHRH), prolactin releasing and inhibiting hormones and MSH releasing and inhibiting hormones. You do not need all of them for the school exam, but GnRH and somatostatin must be known with their effects.

How do these hormones reach the pituitary? The hypothalamic hormones originate in the neurons of the hypothalamus, travel down the axons and are released from the nerve endings, from where they reach the pituitary gland through a portal circulatory system. A portal system is one in which blood collected from one capillary bed is carried by a vein to a second capillary bed instead of returning to the heart. The hypophysial portal vessels collect the releasing and inhibiting hormones from the capillaries in the hypothalamus and deliver them straight to the capillaries of the anterior pituitary, so the hormones reach their target in high concentration without being diluted in the whole blood volume. This is the route for the anterior pituitary only. The posterior pituitary is regulated by the hypothalamus directly through neural connections: the axons of hypothalamic neurons run down into the posterior pituitary and release oxytocin and vasopressin there. So the hypothalamus controls the two lobes of the pituitary by two different routes, portal blood for the anterior lobe and axons for the posterior lobe, and this two-route contrast is a favourite 3-mark question.

The pituitary gland is located in a bony cavity called the sella turcica and is attached to the hypothalamus by a stalk. It is divided anatomically into an adenohypophysis and a neurohypophysis. The adenohypophysis has two portions, the pars distalis and the pars intermedia. The pars distalis, commonly called the anterior pituitary, produces six hormones: growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), luteinising hormone (LH) and follicle stimulating hormone (FSH). The pars intermedia secretes only one hormone, melanocyte stimulating hormone (MSH); in humans the pars intermedia is almost merged with the pars distalis. The neurohypophysis, or pars nervosa, is the posterior pituitary. It stores and releases two hormones, oxytocin and vasopressin, which are actually synthesised by the hypothalamus and are transported axonally to the neurohypophysis. This is the single most examined fact in the chapter: the posterior pituitary releases two hormones but makes neither.

Now the functions, in NCERT order, with the disorder attached to each where there is one. Growth hormone regulates the growth of the body. Its over-secretion stimulates abnormal growth of the body, leading to gigantism; low secretion results in stunted growth, pituitary dwarfism. Excess secretion of GH in adults, especially in middle age, cannot lengthen bones whose growth plates have closed, so it produces severe disfigurement, especially of the face, called acromegaly, which may lead to serious complications and even death if unchecked. Prolactin regulates the growth of the mammary glands and the formation of milk in them. TSH stimulates the synthesis and secretion of thyroid hormones from the thyroid gland. ACTH stimulates the synthesis and secretion of steroid hormones called glucocorticoids from the adrenal cortex. LH and FSH stimulate gonadal activity and are therefore called gonadotrophins. In males, LH stimulates the synthesis and secretion of androgens from the testis, and FSH together with the androgens regulates spermatogenesis. In females, LH induces ovulation of the fully mature follicle (the Graafian follicle) and maintains the corpus luteum formed from the remnants of the follicle after ovulation; FSH stimulates the growth and development of the ovarian follicles. MSH acts on the melanocytes and regulates the pigmentation of the skin.

Oxytocin acts on smooth muscles and stimulates their contraction. In females it stimulates a vigorous contraction of the uterus at the time of child birth and milk ejection from the mammary gland. Vasopressin acts mainly on the kidney and stimulates the reabsorption of water and electrolytes by the distal tubules, thereby reducing the loss of water through urine (diuresis); hence it is also called the anti-diuretic hormone (ADH). Its deficiency reduces water reabsorption, so a large volume of dilute urine is produced (diuresis) and the patient is always thirsty: this is diabetes insipidus. Note that it has nothing to do with insulin or glucose, and the urine contains no sugar, which is the distinction from diabetes mellitus that the examiner tests.

The pineal gland is located on the dorsal side of the forebrain. It secretes a hormone called melatonin. Melatonin plays a very important role in the regulation of the 24-hour (diurnal) rhythm of our body. NCERT gives two examples of that rhythm and you should quote both: it helps in maintaining the normal rhythms of the sleep-wake cycle and of body temperature. In addition, melatonin also influences metabolism, pigmentation, the menstrual cycle and our defence capability. That is the whole NCERT paragraph, and it is enough for the 2-mark question 'name the hormone of the pineal gland and state two of its functions'.

The pineal appears in two exemplar questions that schools like to copy. The first asks which hormone regulates the sleep-wake cycle; the answer is melatonin, and the three distractors offered are usually thyroxine, insulin and adrenaline. The second is the jet-lag question. When you fly across several time zones, the light-dark cycle of the new place is out of step with the body's internal clock. Melatonin secretion, which rises in darkness and falls in light, is still timed to the old place, so you feel sleepy in the day and awake at night. The body clock (the suprachiasmatic nucleus of the hypothalamus, which controls the pineal) adjusts slowly over a few days, and the temporary sleep disturbance during this adjustment is jet lag. The exam answer is: jet lag is a temporary disturbance of the sleep-wake rhythm caused by rapid travel across time zones, because the melatonin rhythm set by the pineal gland is out of phase with the local light-dark cycle until it re-adjusts.

One more fact worth a mark: the pineal is the only endocrine gland whose secretion is directly governed by light, through the eyes and the hypothalamus, which is why it is sometimes called the biological clock of the body.

The thyroid gland is composed of two lobes located on either side of the trachea, interconnected by a thin flap of connective tissue called the isthmus. It is the largest endocrine gland. Under the microscope it is composed of follicles and stromal tissues. Each thyroid follicle is composed of follicular cells enclosing a cavity, and these follicular cells synthesise two hormones, tetraiodothyronine or thyroxine (T₄) and triiodothyronine (T₃). The numbers tell you the iodine content: four atoms in T₄, three in T₃. Iodine is essential for the normal rate of hormone synthesis in the thyroid. Deficiency of iodine in the diet results in hypothyroidism and enlargement of the thyroid gland, commonly called goitre. The gland enlarges because low thyroxine removes the negative feedback on the pituitary, TSH rises, and the over-stimulated follicles multiply and swell even though they cannot make enough hormone.

The disorders form a compact list that every paper draws on. Hypothyroidism during pregnancy causes defective development and maturation of the growing baby, leading to stunted growth (cretinism), mental retardation, low intelligence quotient, abnormal skin and deaf-mutism. In adult women hypothyroidism may cause an irregular menstrual cycle; in adults generally it produces myxoedema, with low BMR, weight gain, lethargy and puffy skin. Due to cancer of the thyroid gland or the development of nodules of the thyroid, the rate of synthesis and secretion of thyroid hormones is increased to abnormal levels, leading to hyperthyroidism, which adversely affects the body physiology. Exophthalmic goitre is a form of hyperthyroidism characterised by enlargement of the thyroid gland, protrusion of the eyeballs, increased basal metabolic rate and weight loss; it is also called Graves' disease. Note the exemplar trap: exophthalmos is the one condition in the list that is not due to thyroid deficiency.

Functions of thyroid hormones, as NCERT lists them: they play an important role in the regulation of the basal metabolic rate; they support the process of red blood cell formation; they control the metabolism of carbohydrates, proteins and fats; and they help maintain water and electrolyte balance. The thyroid also secretes a protein hormone, thyrocalcitonin (TCT) or calcitonin, which regulates the blood calcium level by lowering it. Calcitonin is made by the parafollicular (C) cells between the follicles, not by the follicular cells, and it is a peptide, not an iodothyronine; both distinctions are used in MCQs.

Regulation is a simple negative feedback that examiners like as a flow chart: low T₃/T₄ in blood → hypothalamus releases TRH → anterior pituitary releases TSH → thyroid follicles synthesise and release T₃/T₄ → raised T₃/T₄ inhibits TRH and TSH release.

In humans, four parathyroid glands are present on the back side of the thyroid gland, one pair each in the two lobes of the thyroid gland. They secrete a peptide hormone called parathyroid hormone (PTH), also called parathormone. The secretion of PTH is regulated by the circulating levels of calcium ions: a fall in blood Ca²⁺ stimulates PTH release, a rise suppresses it. There is no pituitary trophic hormone controlling the parathyroid; it senses calcium directly, which is why it is called an independent gland in some questions.

PTH increases the Ca²⁺ level in the blood, and NCERT gives three routes, all three of which are needed for full marks. First, PTH acts on bones and stimulates the process of bone resorption (dissolution or demineralisation), releasing calcium from the skeleton into the blood. Second, PTH stimulates the reabsorption of Ca²⁺ by the renal tubules, so less is lost in urine. Third, it increases Ca²⁺ absorption from the digested food in the intestine (it does this through the activation of vitamin D, which the exemplar mentions). It is thus clear that PTH is a hypercalcemic hormone, that is, it increases the blood Ca²⁺ level. Along with TCT, it plays a significant role in calcium balance in the body.

The pairing with calcitonin is the classic 3-mark or 5-mark question on calcium homeostasis. When blood calcium is high, the thyroid releases calcitonin, which suppresses the release of calcium from bone and lowers blood calcium. When blood calcium is low, the parathyroids release PTH, which raises it by the three routes above. The two hormones are antagonistic and together they hold blood calcium within a narrow range. Why does the body care so much? Because calcium is needed for muscle contraction, nerve impulse transmission, blood clotting and as a second messenger. A fall in blood calcium causes the sustained muscle spasms of tetany that you met in the previous chapter; an excess weakens bones and produces kidney stones.

Hyposecretion of PTH (for instance after accidental removal of the parathyroids in thyroid surgery) causes hypocalcemia and tetany; hypersecretion causes demineralisation of bone and kidney stones. These clinical lines are not in NCERT but appear in school papers as a 1-mark extension.

The thymus gland is a lobular structure located on the dorsal side of the heart and the aorta, behind the sternum. It plays a major role in the development of the immune system. The thymus secretes peptide hormones called thymosins. Thymosins play a major role in the differentiation of T-lymphocytes, which provide cell-mediated immunity. In addition, thymosins also promote the production of antibodies to provide humoral immunity. Both halves of that sentence are marking points; a student who writes only 'T-cells' has given half the answer.

The point examiners like most is the age effect. The thymus is degenerated in old individuals, resulting in a decreased production of thymosins. As a result the immune responses of old persons become weak. This is the NCERT explanation for the exemplar question 'why do old people have a weak immune system', and it also appears as an Assertion-Reason item: Assertion, the immune response in old people is weak; Reason, the thymus degenerates with age and thymosin production falls; both true and R explains A.

Two facts tie this section to the rest of the syllabus. The thymus is a primary lymphoid organ (you will meet that phrase in Class 12, Human Health and Disease), where immature lymphocytes from the bone marrow mature into T-cells. And the exemplar contains a true-or-false statement that B-lymphocytes provide cell-mediated immunity: that statement is false, because B-cells produce antibodies for humoral immunity while T-cells are responsible for cell-mediated immunity. Also note from the exemplar MCQ on calcium: thymosin is the hormone not involved in calcium balance; vitamin D, PTH and thyrocalcitonin are.

Our body has one pair of adrenal glands, one at the anterior part of each kidney (the name means 'upon the kidney', hence suprarenal). The gland is composed of two types of tissues. The centrally located tissue is called the adrenal medulla, and outside this lies the adrenal cortex. The two parts have different origins, different hormones and different chemical classes of hormone, and a 5-mark question expects you to keep them apart.

Adrenal medulla. It secretes two hormones, adrenaline (epinephrine) and noradrenaline (norepinephrine), which are commonly called catecholamines; they are amino-acid derivatives. Adrenaline and noradrenaline are rapidly secreted in response to stress of any kind and during emergency situations, and are called emergency hormones or hormones of fight or flight. NCERT lists their effects and the list is a 3-mark question on its own: they increase alertness, dilate the pupils (pupillary dilation), cause piloerection (raising of hairs), sweating, an increase in heart beat and in the strength of heart contraction, and an increase in the rate of respiration. Catecholamines also stimulate the breakdown of glycogen (glycogenolysis), resulting in an increased concentration of glucose in the blood, and they stimulate the breakdown of lipids and proteins (lipolysis and proteolysis). The picture is of a body being readied for a burst of physical effort: more oxygen, more fuel, more blood flow.

Adrenal cortex. It can be divided into three layers, and NCERT names them from inside out, so be careful when a question asks for the outermost: the zona reticularis (inner layer), the zona fasciculata (middle layer) and the zona glomerulosa (outer layer). The cortex secretes many steroid hormones, commonly called corticoids. The corticoids involved in carbohydrate metabolism are glucocorticoids, and cortisol is the main one in our body. The corticoids that regulate the balance of water and electrolytes are mineralocorticoids, and aldosterone is the main one. Glucocorticoids stimulate gluconeogenesis, lipolysis and proteolysis, and inhibit the cellular uptake and utilisation of amino acids. Cortisol is also involved in maintaining cardio-vascular system and kidney functions, produces anti-inflammatory reactions, suppresses the immune response, and stimulates the production of RBCs. This is why cortisol-like drugs are used for allergies and after transplants. Aldosterone acts mainly on the renal tubules and stimulates the reabsorption of Na⁺ and water and the excretion of K⁺ and phosphate ions; it thus helps maintain electrolytes, body fluid volume, osmotic pressure and blood pressure. Small amounts of androgenic steroids are also secreted by the adrenal cortex, and these play a role in the growth of axial hair, pubic hair and facial hair during puberty.

The pancreas is a composite gland (a heterocrine gland), which acts as both an exocrine and an endocrine gland. The exocrine part, the acini, pours pancreatic juice into the duodenum through a duct, as you studied in digestion. The endocrine pancreas consists of the islets of Langerhans. About 1 to 2 million islets are present in a normal human pancreas, yet they represent only 1 to 2 per cent of the pancreatic tissue. The two main types of cells in the islets are the α-cells, which secrete glucagon, and the β-cells, which secrete insulin. Both hormones are peptides.

Glucagon plays an important role in maintaining the normal blood glucose level. It acts mainly on liver cells (hepatocytes) and stimulates glycogenolysis, the breakdown of glycogen, resulting in an increased blood sugar (hyperglycemia). In addition, it stimulates gluconeogenesis, the synthesis of glucose from non-carbohydrate sources, which also contributes to hyperglycemia. Glucagon reduces the cellular glucose uptake and utilisation. Thus glucagon is a hyperglycemic hormone.

Insulin is a peptide hormone that also regulates glucose homeostasis. It acts mainly on hepatocytes and adipocytes (cells of adipose tissue) and enhances the cellular glucose uptake and utilisation. As a result there is a rapid movement of glucose from blood to the hepatocytes and adipocytes, causing a decrease in blood glucose (hypoglycemia). Insulin also stimulates the conversion of glucose to glycogen (glycogenesis) in the target cells. Insulin is therefore a hypoglycemic hormone. The glucose homeostasis of blood is thus maintained by the joint, antagonistic action of insulin and glucagon: when blood glucose rises after a meal, β-cells release insulin and glucose is stored; when it falls between meals, α-cells release glucagon and the stores are broken down.

Prolonged hyperglycemia leads to a complex disorder called diabetes mellitus, which is associated with the loss of glucose through urine and the formation of harmful compounds known as ketone bodies. Glucose spills into urine because it exceeds the reabsorption capacity of the renal tubules (the renal threshold); ketone bodies form because cells starved of glucose burn fats instead. Diabetic patients are successfully treated with insulin therapy. The exemplar adds a nuance worth knowing: diabetes can result either from an insulin deficiency or from insulin resistance, in which the cells fail to respond to insulin that is present.

A pair of testes is present in the scrotal sac outside the abdomen of male individuals; the scrotum keeps them 2 to 2.5 °C below body temperature, which spermatogenesis needs. The testis performs a dual function: it is a primary sex organ that makes sperms and it is an endocrine gland. It is composed of seminiferous tubules and stromal or interstitial tissue. The Leydig cells or interstitial cells, which are present in the intertubular spaces, produce a group of hormones called androgens, mainly testosterone. Androgens are steroids.

NCERT gives the functions of androgens in one long sentence that you should split into points for a 3-mark answer. Androgens regulate the development, maturation and functions of the male accessory sex organs: the epididymis, vas deferens, seminal vesicles, prostate gland and urethra. They stimulate muscular growth, the growth of facial and axillary hair, aggressiveness and a low pitch of voice, that is, the male secondary sexual characters. They play a major stimulatory role in the process of spermatogenesis. They act on the central neural system and influence male sexual behaviour (libido). And they produce anabolic (synthetic) effects on protein and carbohydrate metabolism, which is the reason they are misused as performance-enhancing drugs, a point Class 12 returns to.

Control of the testis is by the pituitary gonadotrophins, and the exemplar asks the roles of LH in both sexes. In males, LH acts on the Leydig cells and stimulates the synthesis and secretion of androgens; FSH acts on the seminiferous tubules and, together with androgens, regulates spermatogenesis. The hypothalamus starts the chain with GnRH, and testosterone in turn inhibits GnRH and LH by negative feedback. The exercise question on the mechanism of action of FSH fits here: FSH is a protein (glycoprotein) hormone, so it binds to membrane receptors on its target cells, the Sertoli cells of the seminiferous tubules in males and the follicle cells of the ovary in females, generates a second messenger (cyclic AMP) inside the cell, and the second messenger activates the enzymes that carry out the cell's response, spermatogenesis in the testis and growth of the follicle in the ovary.

Females have a pair of ovaries located in the abdomen (the pelvic cavity). The ovary is the primary female sex organ, which produces one ovum during each menstrual cycle, and it is an endocrine gland. The ovary is composed of ovarian follicles and stromal tissues. It produces two groups of steroid hormones, estrogen and progesterone, and the timing of their secretion is what the examiner wants. Estrogen is synthesised and secreted mainly by the growing ovarian follicles. After ovulation, the ruptured follicle is converted to a structure called the corpus luteum, which secretes mainly progesterone. So follicle means estrogen and corpus luteum means progesterone; the exemplar MCQ 'the corpus luteum secretes' has progesterone as its answer.

Estrogens produce wide-ranging actions such as the stimulation of growth and activities of the female secondary sex organs (uterus, fallopian tubes, vagina), the development of growing ovarian follicles, the appearance of female secondary sex characters (for example a high pitch of voice, breast development, the pattern of fat and hair), and the development of mammary glands. Estrogens also regulate female sexual behaviour. Progesterone supports pregnancy: it prepares and maintains the uterine endometrium for the implanted embryo and suppresses uterine contractions. Progesterone also acts on the mammary glands and stimulates the formation of alveoli (sac-like structures which store milk) and milk secretion. NCERT calls it the progestational hormone in exercise 6, and that is the term the answer wants.

Control is again by the gonadotrophins, and the exemplar's feedback question is the cleverest thing set from this section. FSH stimulates the growth and development of ovarian follicles; the growing follicles secrete estrogen; LH induces ovulation of the fully mature Graafian follicle and maintains the corpus luteum. Rising estrogen normally feeds back to reduce LH secretion. Now the two clinical cases: an old woman whose blood shows high LH but low estrogen has ovaries (the gland X) that no longer respond to LH, as happens after menopause when the follicles are exhausted, so the pituitary keeps pushing without result. A woman with high LH and high estrogen has a defect in the negative feedback loop, because her high estrogen is failing to switch LH off.

As mentioned earlier, hormones are also secreted by some tissues which are not endocrine glands. This short section produces a surprising number of 1-mark questions, because each organ has one hormone with one crisp function.

Heart. The atrial wall of our heart secretes a very important 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; this reduces the blood pressure. 'Natriuretic' means it also promotes the excretion of sodium in urine, which lowers blood volume. ANF is the 'blood pressure lowering hormone' of exercise 6(e) and it works in the opposite direction to aldosterone and vasopressin.

Kidney. The juxtaglomerular cells of the kidney produce a peptide hormone called erythropoietin, which stimulates erythropoiesis, the formation of RBCs, in the bone marrow. It is released when the oxygen supply to the kidney falls, which is why people living at high altitude have more red cells and why kidney failure causes anaemia. Keep erythropoietin distinct from renin, an enzyme from the same cells that you met in the excretion chapter.

Gastrointestinal tract. Endocrine cells present in different parts of the GI tract secrete four major peptide hormones. Gastrin acts on the gastric glands and stimulates the secretion of hydrochloric acid and pepsinogen. Secretin acts on the exocrine pancreas and stimulates the secretion of water and bicarbonate ions, which neutralise the acid chyme entering the duodenum. Cholecystokinin (CCK) acts on both the pancreas and the gall bladder and stimulates the secretion of pancreatic enzymes and bile juice respectively. Gastric inhibitory peptide (GIP) inhibits gastric secretion and motility. Read the names as instructions: gastr-in stimulates the gastric glands, secret-in makes the pancreas secrete, chole-cysto-kinin moves the bile bladder, and gastric inhibitory peptide inhibits the stomach.

Finally NCERT notes that several non-endocrine tissues secrete hormones called growth factors, which are essential for the normal growth of tissues and their repair or regeneration. This is the reason the definition of a hormone was widened in section 19.1.

Hormones produce their effects on target tissues by binding to specific proteins called hormone receptors located in the target tissues only. Receptors are of two kinds. Membrane-bound receptors are present on the cell membrane of the target cells. Intracellular receptors are present inside the target cell, mostly in the nucleus, and are therefore also called nuclear receptors. The binding of a hormone to its receptor leads to the formation of a hormone-receptor complex. Each receptor is specific to one hormone only, and hence receptors are said to be specific. That specificity is the reason a hormone circulating in the whole blood acts only on its target cells: only they carry the receptor. The formation of the hormone-receptor complex leads to certain biochemical changes in the target tissue, and target tissue metabolism and hence physiological functions are regulated by hormones.

On the basis of their chemical nature, hormones can be divided into four groups, and this classification decides which kind of receptor a hormone uses. (i) Peptide, polypeptide and protein hormones: insulin, glucagon, the pituitary hormones, the hypothalamic hormones (and also PTH, calcitonin, thymosins, ANF, erythropoietin and the gut hormones). (ii) Steroids: cortisol, aldosterone, testosterone, estradiol and progesterone. (iii) Iodothyronines: the thyroid hormones T₃ and T₄. (iv) Amino-acid derivatives: epinephrine and norepinephrine (and melatonin).

Protein and peptide hormones are water-soluble and cannot cross the lipid bilayer, so they act through membrane-bound receptors. The hormone (the first messenger) binds to the receptor on the outer surface; the complex activates an enzyme inside the membrane (adenylate cyclase for the cAMP pathway), which generates a second messenger inside the cell. NCERT names three second messengers: cyclic AMP, IP₃ (inositol trisphosphate) and Ca²⁺. The second messenger activates a cascade of enzymes (protein kinases), which in turn regulate cellular metabolism, so the hormone's message is amplified and delivered without the hormone ever entering the cell. This is NCERT Fig. 19.5(a) and it must be drawn as: hormone → membrane receptor → second messenger (cAMP) → biochemical responses (enzyme activation) → physiological response.

Steroid hormones and iodothyronines are lipid-soluble and pass through the plasma membrane. Inside the cell they bind to intracellular receptors, and the hormone-receptor complex enters the nucleus and interacts with the genome (DNA). This interaction regulates gene expression or chromosome function, switching particular genes on or off. Cumulative biochemical actions, the synthesis of new proteins directed by the switched-on genes, result in physiological and developmental effects. This is Fig. 19.5(b): hormone → intracellular receptor → hormone-receptor complex → genome interaction → gene expression (protein synthesis) → physiological and developmental effects. The two mechanisms differ in speed too: second-messenger responses are fast (adrenaline acts within seconds), gene-expression responses are slow but long lasting (thyroxine and testosterone act over days).