Hormones and the Endocrine System: IB C3.1, D3.3 and NEET

1 Endocrine glands and hormones

Syllabus link: NCERT XI 19.1 Endocrine glands and hormones; IB C3.1.3 (SL) hormonal and nervous signalling; IB C2.1.3 to C2.1.5 HL

The nervous system and the endocrine system jointly coordinate and regulate the physiological functions of the body. The neural system provides point-to-point, rapid coordination among organs, but it is short-lived. Nerve fibres do not reach every cell, and many cellular functions need continuous regulation. Hormones do that job. This chapter explains how the human endocrine system works, gland by gland, for IB Biology and NEET.

Nervous system vs endocrine system

The nervous system and the endocrine system both carry messages between organs, but they do it in very different ways. IB asks you to distinguish them; NEET expects the same basic contrast. For a plain-language overview, see the MedlinePlus guide to the endocrine system.

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Glands of the endocrine system: endocrine vs exocrine

An exocrine gland has a duct. Its epithelial cells secrete into the duct, which carries the secretion to a body surface or into a cavity (e.g. salivary glands into the mouth, sweat glands onto the skin).

Endocrine glands are ductless. Their secretory epithelial cells release hormones into the surrounding tissue fluid, from where they enter the blood capillaries that run through the gland and travel to the rest of the body.

What is a hormone? The messengers of the endocrine system

NCERT defines hormones as non-nutrient chemicals which act as intercellular messengers and are produced in trace amounts. “Non-nutrient” means they are not used as food or as a source of energy or raw material; it does not mean they cannot be swallowed. Thyroxine tablets, oral steroids and contraceptive pills all work when taken by mouth, although protein hormones such as insulin are digested in the gut and must be injected.

The word hormone comes from the Greek hormaein, “to excite or set in motion”. Many hormones are inhibitory, though; the name simply dates from when the first ones were discovered. Invertebrates have simple endocrine systems with few hormones, while vertebrates use a large number of chemicals as hormones.

Chemical nature of hormones

Hormones of the endocrine system belong to four chemical groups. The chemical group of a hormone decides whether it can cross the plasma membrane, and so how it acts (section 9). Peptide hormones are made on the rough ER, packaged by the Golgi apparatus into vesicles and released by exocytosis; steroid hormones are made from cholesterol.

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2 Hypothalamus and pituitary gland

Syllabus link: NCERT XI 19.2.1 The hypothalamus, 19.2.2 The pituitary gland; IB C3.1.13 (SL) control of the endocrine system by the hypothalamus and pituitary gland

The hypothalamus links the nervous system to the endocrine system. It monitors the blood (temperature, osmotic concentration, hormone levels) and controls the pituitary gland, which in turn controls several other endocrine glands, so the pair sit at the top of the human endocrine system.

The hypothalamus

• It is the basal part (floor) of the diencephalon of the forebrain.
• It contains several groups of neurosecretory cells called nuclei: neurons that secrete hormones (neurohormones).
• Its hormones pass to the pituitary gland and regulate the synthesis and secretion of pituitary hormones.
• It is also part of the limbic system and controls the autonomic nervous system, body temperature, thirst and hunger.

A stalk (the infundibulum) connects the hypothalamus to the pituitary gland, which sits in a bony cavity of the sphenoid bone called the sella turcica. The hypothalamus reaches the two lobes of the pituitary in two different ways:

• Anterior pituitary: neurosecretory cells release releasing and inhibiting hormones into a capillary bed in the hypothalamus. Blood from the superior hypophyseal arteries (branches of the internal carotid artery) carries them down the hypophyseal portal vein to a second capillary bed in the anterior pituitary.
• Posterior pituitary: the axons of some neurosecretory cells run down the stalk into the posterior pituitary (neurohypophysis) and release their hormones there, straight into the blood.

A portal vein is a vein that begins in one capillary bed and ends in a second capillary bed instead of going straight to the heart. The hypophyseal portal system lets hypothalamic hormones reach the anterior pituitary in high concentration, without being diluted in the general circulation.

Hypothalamic releasing and inhibiting hormones

Hypothalamic hormones are either releasing hormones, which stimulate the pituitary to secrete a hormone, or inhibiting hormones, which stop it. NCERT gives GnRH and somatostatin as examples; NEET books list seven:

• GHRH (growth hormone-releasing hormone): stimulates the anterior pituitary to release growth hormone.
• GHIH (growth hormone-inhibiting hormone), also called somatostatin: inhibits the release of growth hormone.
• TRH (thyrotropin-releasing hormone): stimulates the anterior pituitary to release TSH (thyroid-stimulating hormone).
• GnRH (gonadotropin-releasing hormone): stimulates the anterior pituitary to release the gonadotropins FSH and LH.
• CRH (corticotropin-releasing hormone): stimulates the anterior pituitary to release ACTH (adrenocorticotropic hormone).
• PRH (prolactin-releasing hormone): stimulates the anterior pituitary to release prolactin.
• PIH (prolactin-inhibiting hormone), which is dopamine: inhibits the release of prolactin.

Posterior pituitary hormones: made in the hypothalamus

Two hormones are made in the hypothalamus, carried down the axons and only stored and released by the posterior pituitary (neurohypophysis):

• Oxytocin, made mainly by the paraventricular nuclei: contracts the smooth muscle of the uterus during childbirth and causes milk ejection from the mammary glands. A synthetic form (Pitocin) is used to induce labour.
• Vasopressin (ADH, antidiuretic hormone), made mainly by the supraoptic nuclei: increases water reabsorption in the late DCT and collecting duct of the kidney. Too little ADH causes diabetes insipidus: large volumes of dilute urine and great thirst. See Human Excretory System: ADH, RAAS and ANF for how ADH and aquaporins work.

Both nuclei make some of each hormone; “mainly” is the accurate word.

The pituitary gland: master gland of the endocrine system

• Also called the hypophysis; a small, pea-sized gland in the sella turcica.
• Called the master gland because its hormones control several other endocrine glands, though it is itself controlled by the hypothalamus.
• Divided into the adenohypophysis and the neurohypophysis (pars nervosa). The adenohypophysis has two parts: pars distalis (anterior pituitary) and pars intermedia, which in adult humans is almost merged with the pars distalis.
• It is ectodermal in origin, from two sources: the anterior lobe grows up from the roof of the embryo’s mouth (Rathke’s pouch), and the posterior lobe grows down from the brain (the floor of the diencephalon).
• It secretes trophic (tropic) hormones, which stimulate other endocrine glands, and non-trophic hormones, which act directly on non-endocrine tissues.

Trophic hormones of the anterior pituitary

These act on other endocrine glands:

• TSH (thyroid-stimulating hormone, thyrotropin): stimulates the thyroid gland to secrete T3 and T4.
• FSH (follicle-stimulating hormone): in females, stimulates growth and development of ovarian follicles; in males, with androgens, regulates spermatogenesis.
• LH (luteinising hormone): in females, induces ovulation and maintains the corpus luteum; in males, stimulates the Leydig cells to secrete androgens.
• ACTH (adrenocorticotropic hormone): stimulates the adrenal cortex to secrete glucocorticoids.

Non-trophic hormones of the anterior and intermediate lobes

These act directly on non-endocrine tissues:

• GH (growth hormone, somatotropin): increases protein synthesis and raises blood glucose. Much of its growth effect works through an intermediate: GH makes the liver release somatomedins, chiefly IGF-1 (insulin-like growth factor 1). IGF-1 is anabolic: it binds to cells of bone, cartilage, skeletal muscle and other tissues and promotes cell division and protein synthesis, so the body grows. GH also acts directly on fat cells, promoting lipolysis (fat breakdown), which supplies energy between meals and during fasting. GH is still secreted in adults, where it maintains and repairs tissues.
• Prolactin (PRL): stimulates the growth of the mammary glands and milk production. Prolactin levels rise steadily during pregnancy, but high progesterone and estrogen hold back milk secretion until after birth. Its release is stimulated by PRH and inhibited by PIH (dopamine).
• MSH (melanocyte-stimulating hormone): the only hormone of the pars intermedia (NCERT). It acts on melanocytes in the skin and regulates pigmentation.

Growth hormone disorders

• Pituitary dwarfism: too little GH in childhood; stunted but proportionate growth.
• Gigantism: too much GH in childhood, before the growth plates (epiphyses) close; abnormal increase in height.
• Acromegaly: too much GH in adults, especially in middle age. The growth plates have already closed, so bones cannot lengthen; instead they thicken and enlarge, especially the hands, feet, jaw and face, causing severe disfigurement.

3 Thyroid, parathyroid and adrenal glands

Syllabus link: NCERT XI 19.2.4 Thyroid, 19.2.5 Parathyroid, 19.2.7 Adrenal gland; IB C3.1.12 (SL) adrenaline; IB D3.3.5 (SL) thyroxin

These three glands of the endocrine system control metabolic rate, blood calcium, salt and water balance, the stress response and the response to emergencies.

Thyroid gland

• The largest gland of the human endocrine system; butterfly-shaped.
• Two lobes lie on either side of the trachea, just below the larynx, joined by a thin flap of tissue called the isthmus.
• Each lobe is made of many follicles, the structural and functional units, richly supplied with blood vessels.
• Follicles are lined by cuboidal epithelium and filled with a gelatinous colloid (stored thyroglobulin).
• Follicular cells secrete T3 (triiodothyronine) and T4 (tetraiodothyronine or thyroxine), both made by iodination of the amino acid tyrosine.
• Parafollicular (C) cells, between the follicles, secrete thyrocalcitonin (TCT), which lowers blood Ca²⁺.

Secretion is controlled by the hypothalamus and pituitary: TRH (hypothalamus) → TSH (anterior pituitary) → T3 and T4 (thyroid). When T3 and T4 rise in the blood they feed back negatively on both the hypothalamus and the pituitary, reducing TRH and TSH (see the TRH–TSH feedback diagram in section 7).

Functions of T3 and T4

The thyroid releases much more T4 than T3, but T3 is the more active form: most T4 is converted to T3 in the tissues. Thyroid hormones act on almost every cell.

• Regulate the basal metabolic rate (BMR), the minimum energy use needed to stay alive. They increase cell respiration of carbohydrates, fats and amino acids, so energy and heat production rise.
• Increase protein synthesis; essential for normal physical and mental growth.
• Support the process of red blood cell formation.
• Control the metabolism of carbohydrates, proteins and fats.
• Help maintain water and electrolyte balance.
• Needed for a normal menstrual cycle.
• In amphibians, needed for metamorphosis of the tadpole into an adult frog.

Hypothyroidism: too little T3 and T4

• Cretinism: hypothyroidism during pregnancy or in infancy causes defective development of the baby: stunted growth, mental retardation and low IQ, abnormal skin, a protruding belly and thick tongue, and deaf-mutism.
• Myxoedema Beyond the syllabus: hypothyroidism in adults. Puffy appearance, low BMR, weight gain, lethargy and sensitivity to cold; in women the menstrual cycle may become irregular. Treated with daily thyroxine tablets.
• Hashimoto’s thyroiditis Beyond the syllabus: an autoimmune disease in which the immune system attacks and damages the thyroid, so it cannot make enough hormone.
• Simple goitre: enlargement of the thyroid caused by iodine deficiency in the diet. It is common in hilly regions where rain washes iodine out of the soil, so local crops contain little iodine. With too little iodine, little T3/T4 is made; negative feedback weakens, so TSH stays high and keeps stimulating the gland, which enlarges. Iodised salt prevents it.

Hyperthyroidism: too much T3 and T4

• BMR rises; the person loses weight, feels nervous and cannot tolerate heat.
• Caused by thyroid tumours or nodules, or by Graves’ disease.
• Graves’ disease (exophthalmic goitre): an autoimmune disease. Antibodies bind to and stimulate the TSH receptor, so the thyroid keeps secreting even when TSH is low. The gland enlarges and the eyeballs protrude because the tissues behind the eyes swell.
• Beyond the syllabus Treatment includes antithyroid drugs such as thiourea-type drugs (carbimazole, propylthiouracil), which block the synthesis of thyroid hormones.

Thyrocalcitonin (TCT)

• A peptide hormone of 32 amino acids, secreted by the parafollicular cells.
• Released when blood calcium is high (hypercalcaemia).
• Lowers blood Ca²⁺ mainly by inhibiting osteoclasts, the large multinucleate cells that break down bone, and by increasing Ca²⁺ excretion by the kidneys.
• No disorder of calcitonin deficiency is known.

Parathyroid glands

• Humans have four parathyroid glands on the back surface of the thyroid, one pair on each lobe.
• They secrete parathyroid hormone (PTH, parathormone), a peptide hormone, when blood Ca²⁺ falls (hypocalcaemia). Its action is antagonistic to calcitonin.
• PTH raises blood Ca²⁺: it stimulates bone resorption (osteoclasts dissolve bone mineral), increases Ca²⁺ reabsorption in the kidney tubules, and stimulates the kidney to make calcitriol (active vitamin D, 1,25-dihydroxycholecalciferol) from inactive vitamin D. Calcitriol then increases Ca²⁺ absorption from digested food in the gut.
• PTH is therefore a hypercalcaemic hormone.

Too little PTH: hypocalcaemic tetany

Calcium ions on the outside of nerve cell membranes help keep voltage-gated Na⁺ channels closed at rest. When blood Ca²⁺ falls, these channels open much more easily, so nerves and muscles become over-excitable and fire on their own. The result is tetany: twitching, cramps and sustained spasms of skeletal muscles, typically of the hands and feet (carpal spasm). Blood Na⁺ and K⁺ do not rise; the cause is the low Ca²⁺.

Too much PTH: hyperparathyroidism Beyond the syllabus

Osteoclast activity rises and bones lose calcium (demineralisation), becoming fragile and fracturing easily; in severe cases the bone matrix is replaced by fibrous tissue and cysts (osteitis fibrosa cystica). The high blood Ca²⁺ can also cause kidney stones.

Adrenal glands

• A pair of glands, one on top of each kidney; also called suprarenal glands.
• Two distinct regions: the central adrenal medulla (from neural crest, ectoderm) and the outer adrenal cortex (from mesoderm).

Adrenal medulla: adrenaline for vigorous activity

The adrenal medulla secretes adrenaline (epinephrine) and noradrenaline (norepinephrine), together called catecholamines; about 80% is adrenaline. They are secreted rapidly in response to stress and emergencies, so they are called the emergency hormones or hormones of fight or flight (fright, fight and flight).

Adrenaline prepares the body for vigorous activity (IB C3.1.12):

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Noradrenaline’s main effect is vasoconstriction throughout the body, which raises blood pressure. The sympathetic nervous system releases noradrenaline from its nerve endings and works together with the adrenal medulla (the sympathetico-adrenal system), a clear example of the nervous system and endocrine system working together; the parasympathetic system has the opposite effects at rest.

Adrenal cortex

The cortex has three zones, from the outside in: zona glomerulosa, zona fasciculata and zona reticularis. Together they make more than 20 hormones, all steroids (corticoids), grouped by function:

• Zona glomerulosa: mineralocorticoids (mainly aldosterone): salt and water balance.
• Zona fasciculata: glucocorticoids (mainly cortisol): glucose metabolism and stress.
• Zona reticularis: sex corticoids, mainly weak androgens.

Mineralocorticoids: aldosterone

• Made in the zona glomerulosa; the main one is aldosterone.
• Released when blood pressure or blood volume falls, when blood Na⁺ is low or blood K⁺ is high, and when the renin-angiotensin-aldosterone system (RAAS) is activated.
• Acts on the late DCT and collecting duct: increases Na⁺ reabsorption (water follows) and K⁺ and phosphate excretion.
• So it maintains electrolytes, body fluid volume, osmotic pressure and blood pressure.

Glucocorticoids: cortisol

The glucocorticoids are cortisol, cortisone and corticosterone; cortisol is the most important. They are released in response to ACTH, especially during stress.

• Raise blood glucose mainly by gluconeogenesis (making new glucose from amino acids and glycerol), with lipolysis and proteolysis supplying the raw materials. They also inhibit the uptake and use of amino acids by cells.
• Glucose-sparing effect: cortisol makes most cells use fatty acids and amino acids for respiration instead of glucose, saving glucose for the brain, which depends on it. (In the liver cortisol actually promotes glycogen storage; glycogen breakdown is the job of glucagon and adrenaline.)
• Anti-inflammatory: blocks the effects of histamine and stabilises lysosome membranes, limiting tissue damage; also anti-allergic.
• Suppresses the immune response (fewer lymphocytes) and stimulates RBC production.
• Helps the body cope with long-term stress; maintains the cardiovascular system and kidney function.
• In large doses inhibits growth and increases bone resorption.

Sex corticoids

• Made in the zona reticularis in response to ACTH.
• Mainly weak androgens such as DHEA (dehydroepiandrosterone); only a little estrogen is formed, mostly by conversion in other tissues.
• Role: growth of axial (armpit), pubic and facial hair during puberty (NCERT).

Disorders of the adrenal cortex

• Addison’s disease (NEET list): failure of the adrenal cortex, so both cortisol and aldosterone are too low. Low cortisol alters carbohydrate metabolism and causes acute weakness, fatigue and low blood glucose; low aldosterone causes low blood Na⁺, high K⁺, dehydration and low blood pressure. The skin shows a bronze pigmentation, because the pituitary makes extra ACTH, which also stimulates melanocytes.
• Conn’s syndrome Beyond the syllabus: too much aldosterone, usually from a tumour. Na⁺ and water are retained, causing high blood pressure; K⁺ is lost, causing muscle weakness and cramps.
• Cushing’s syndrome Beyond the syllabus: too much cortisol, from a cortex tumour, excess ACTH or long-term steroid drugs. Features: high blood glucose, fat redistributed to the abdomen (pendulous belly), face (moon face) and upper back (buffalo hump), purple stretch marks (striae), excess hair (hirsutism), amenorrhoea and slow wound healing.

4 Pineal, thymus, gonads and other hormone sources

Syllabus link: NCERT XI 19.2.3 Pineal gland, 19.2.6 Thymus, 19.2.9 Testis, 19.2.10 Ovary, 19.3 Hormones of heart, kidney and gastrointestinal tract; IB C3.1.11 (SL) melatonin

The human endocrine system also includes the pineal gland, the thymus and the gonads, plus hormone-secreting cells in the heart, kidney and gut. All are in the NEET syllabus, and the pineal gland’s melatonin is an IB SL statement.

Pineal gland and melatonin

• Also called the epiphysis cerebri; a small pine-cone-shaped gland on the dorsal side of the forebrain (roof of the diencephalon, behind the third ventricle).
• Secretes melatonin, an amine hormone made from the amino acid tryptophan (through serotonin).
• Melatonin regulates the 24-hour (diurnal) rhythm of the body: the sleep-wake cycle and body temperature. It also influences metabolism, pigmentation, the menstrual cycle and our defence capability (NCERT).

How melatonin sets the sleep cycle (IB C3.1.11): light falling on the retina sends nerve impulses to the suprachiasmatic nucleus (SCN) of the hypothalamus, the body’s master clock. From the SCN, a pathway through the spinal cord and sympathetic nerves reaches the pineal gland and inhibits melatonin secretion. So melatonin is low in daylight and we stay awake. As light fades in the evening the inhibition stops, melatonin rises, peaks in the middle of the night and makes us drowsy; it falls again towards morning.

Thymus

• A lobular gland between the lungs, behind the sternum and on the front of the aorta (in the mediastinum).
• Large in childhood; it shrinks after puberty and in old age is largely replaced by fat.
• Secretes peptide hormones, thymosins, which help T lymphocytes differentiate (cell-mediated immunity) and also promote antibody production (humoral immunity).
• Because the thymus degenerates in old age, thymosin production falls and immune responses weaken (NCERT).

Testes

• A pair of testes in the scrotum. They are both gametogenic and endocrine glands (sometimes called heterocrine).
• Leydig (interstitial) cells between the seminiferous tubules secrete androgens, mainly testosterone, an anabolic steroid. Sertoli cells in the tubules secrete inhibin, which inhibits FSH secretion.
• Beyond the syllabus Misuse of anabolic steroids (synthetic testosterone) causes acne and, through negative feedback that reduces LH and FSH, a fall in sperm count.

Ovaries

• A pair of ovaries in the abdomen; they produce ova and hormones.
• Growing ovarian follicles secrete estrogen (mainly estradiol).
• After ovulation, the ruptured follicle becomes the corpus luteum, which secretes mainly progesterone.
• Late in pregnancy the ovary also secretes relaxin, which softens the ligaments of the pelvis and the cervix for birth (NCERT XII, Human Reproduction).

Hormones of the heart, kidney and gut: the diffuse endocrine system

Some tissues that are not endocrine glands also secrete hormones (NCERT 19.3), so the endocrine system is wider than its glands.

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Beyond NCERT: most EPO actually comes from interstitial cells around the kidney tubules, but NCERT and NEET credit the juxtaglomerular cells. More on the gut hormones: Digestion and Absorption: hormonal control. More on ANF and renin: the renin-angiotensin-aldosterone system.

5 Pancreas and regulation of blood glucose

Syllabus link: NCERT XI 19.2.8 Pancreas; IB D3.3.1 to D3.3.3 (SL) homeostasis and regulation of blood glucose

Blood glucose is a homeostatic variable: it is kept close to a set point of about 5 mmol L⁻¹ (90 mg dL⁻¹) despite meals, fasting and exercise. Too high damages blood vessels and nerves; too low starves the brain. The pancreas controls it by negative feedback, the best-known example of the endocrine system in homeostasis.

The pancreas: a mixed gland

• The pancreas is both exocrine (pancreatic juice with enzymes, into the duodenum) and endocrine.
• The endocrine part is the islets of Langerhans: about 1 to 2 million clusters of cells, only 1 to 2% of the pancreatic tissue. See pancreatic juice and the digestive glands for the exocrine part.
• α (alpha) cells secrete glucagon; β (beta) cells secrete insulin.
• Beyond the syllabus δ (delta) cells secrete somatostatin, which inhibits the release of both insulin and glucagon; PP cells secrete pancreatic polypeptide, which inhibits the secretion of pancreatic (exocrine) juice.

The blood glucose control loop

1. The islet cells themselves are the receptors: they detect the glucose concentration of the blood flowing through the pancreas.
2. If glucose rises, β cells secrete insulin into the blood. Its targets are liver cells, skeletal muscle cells and adipose (fat) cells, which take up glucose and store it as glycogen or fat.
3. If glucose falls, α cells secrete glucagon. Its main target is the liver, which breaks down glycogen and makes new glucose, then releases glucose into the blood.
4. In each case the response cancels the change: negative feedback returns blood glucose to the set point.
5. Insulin and glucagon are antagonistic hormones: they have opposite effects on the same variable.

6 Insulin and glucagon

Syllabus link: NCERT XI 19.2.8 Pancreas; IB D3.3.3 (SL) effects on target cells; IB C2.1.11 HL insulin receptor with tyrosine kinase activity

Insulin and glucagon are the two endocrine system hormones that matter most for blood glucose. Both are peptide hormones from the islets of Langerhans, carried in the blood plasma to their target cells.

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IB only HL Cell signalling: how insulin and adrenaline act

In the endocrine system, a signalling chemical is called a ligand; its receptor is a protein with a binding site specific to that ligand. Binding starts a signal transduction pathway inside the cell.

• Transmembrane receptors span the plasma membrane: their outside has hydrophilic amino acids and the part crossing the membrane has hydrophobic ones. They bind hydrophilic ligands (peptides, adrenaline) that cannot enter the cell.
• Intracellular receptors in the cytoplasm or nucleus bind hydrophobic ligands (steroids) that diffuse through the membrane (section 9).
• Adrenaline binds a G protein-coupled receptor. The activated G protein switches on adenylyl cyclase, which makes cyclic AMP (cAMP), the second messenger; cAMP activates protein kinase A, leading, in liver and muscle, to glycogen breakdown.
• Insulin binds a receptor with tyrosine kinase activity. Tyrosines on the inside of the receptor become phosphorylated, a chain of reactions follows, and vesicles carrying GLUT4 glucose transporters move to and fuse with the plasma membrane, so more glucose enters the cell.

7 Hormonal control of growth and metabolism

Syllabus link: NCERT XI 19.2 (GH, thyroid hormones, glucocorticoids); IB D3.3.5 and D3.3.6 (SL) thermoregulation with thyroxin

The endocrine system controls growth and metabolism through several hormones acting together. GH and thyroxine are the main growth hormones; insulin, glucagon, adrenaline and cortisol decide whether fuel is stored or used.

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Thyroxine, metabolic rate and body temperature

Body temperature is another homeostatic variable controlled by negative feedback (IB D3.3.5); here the nervous system and the endocrine system act together. Peripheral thermoreceptors in the skin and receptors in the hypothalamus detect temperature changes. When the body is cold, the hypothalamus increases TRH, the pituitary releases more TSH and the thyroid releases more thyroxin. Thyroxin raises the metabolic rate of cells, so more heat is released by respiration. Other effectors work at the same time:

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IB D3.3.6 asks for these human thermoregulation mechanisms; they are covered again in the Homeostasis chapter (card 9 of Human Physiology).

8 Hormonal feedback mechanisms

Syllabus link: IB D3.3.2 (SL) negative feedback loops; IB D3.1.5 (SL) positive and negative feedback in the menstrual cycle; IB C2.1.14 HL; NCERT XI 19.2 (feedback control of hormone secretion)

Feedback is how the endocrine system controls itself. Most hormone secretion is controlled by feedback: the result of a hormone’s action changes how much of the hormone is secreted.

Negative feedback in the endocrine system

In negative feedback the response reverses the change that caused it. If a variable rises above its set point, the response lowers it; if it falls below, the response raises it. This keeps homeostatic variables within narrow limits.

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Many hypothalamus-pituitary axes work by long-loop negative feedback: the final hormone (thyroxine, cortisol, testosterone, estradiol) inhibits both the hypothalamus and the anterior pituitary. This is the commonest control pattern in the human endocrine system.

Positive feedback

In positive feedback the response increases the change, so it grows until some outside event ends it. The endocrine system uses it for changes that need to be completed quickly, not for homeostasis.

• Childbirth: stretching of the cervix → more oxytocin → stronger uterine contractions → more stretching, until the baby is born.
• The LH surge: before ovulation, high oestradiol switches from negative to positive feedback on the hypothalamus and pituitary, causing a surge of LH that triggers ovulation.
• Milk ejection: suckling → oxytocin → milk let-down → more suckling.

Antagonistic and synergistic hormones

Hormones of the endocrine system often act in pairs or teams.

• Antagonistic hormones have opposite effects on the same variable: insulin and glucagon (blood glucose), calcitonin and PTH (blood Ca²⁺).
• Synergistic hormones work together to produce a bigger combined effect: estrogen, progesterone, prolactin and oxytocin together prepare the mammary glands and produce and eject milk; glucagon, adrenaline and cortisol together raise blood glucose.

9 Mechanism of hormone action

Syllabus link: NCERT XI 19.4 Mechanism of hormone action (elementary idea); IB C2.1.6 to C2.1.13 HL

Hormones of the endocrine system travel in the blood to every cell, but only target cells respond, because only they have receptors for that hormone. A hormone binding to its receptor forms a hormone-receptor complex, and each receptor is specific to one hormone. The hormone is the first messenger.

• Membrane-bound receptors are on the plasma membrane of target cells. They bind water-soluble hormones (peptides, proteins, catecholamines), which cannot cross the lipid bilayer.
• Intracellular receptors are inside the cell, mostly in the nucleus (nuclear receptors). They bind lipid-soluble hormones: steroids (corticoids, testosterone, estrogen, progesterone) and iodothyronines (T3, T4), which diffuse through the membrane.

Lipid-soluble hormones: steroids and thyroid hormones

1. The hormone diffuses through the plasma membrane into the target cell.
2. It binds a receptor protein in the cytoplasm or nucleus to form a hormone-receptor complex.
3. The complex binds a specific DNA sequence in the nucleus.
4. Transcription of particular genes is switched on (or off), making mRNA.
5. The mRNA is translated into new proteins, such as enzymes or membrane channels, which change the cell’s activity.

Because they work through gene expression, these hormones act more slowly but their effects last longer, which is typical of the endocrine system.

Water-soluble hormones: second messengers

These hormones do not enter the cell. The receptor passes the signal inside:

1. The hormone binds its membrane receptor.
2. The receptor activates a G protein on the inside of the membrane; the G protein has α, β and γ subunits, and the α subunit swaps its GDP for GTP.
3. The activated G protein activates the enzyme adenylate cyclase.
4. Adenylate cyclase converts ATP into cyclic AMP (cAMP) + pyrophosphate (PP_i).
5. cAMP is the second messenger. It activates protein kinase, which was present in an inactive form.
6. The protein kinase phosphorylates other enzymes, setting off the reactions that make up the cell’s response. One hormone molecule can lead to millions of product molecules (amplification).

• Common second messengers: cAMP, cGMP, IP₃ (inositol trisphosphate), DAG (diacylglycerol) and Ca²⁺. IP₃ and DAG are made by splitting the membrane lipid PIP₂, which is their precursor, not a messenger itself.
• Insulin is different: its receptor is itself an enzyme (a receptor tyrosine kinase), not a G protein-coupled receptor (see the IB box in section 6).

10 Diabetes mellitus and selected endocrine disorders

Syllabus link: NCERT XI 19.2 (hypo- and hyperactivity disorders: dwarfism, acromegaly, cretinism, goitre, exophthalmic goitre, diabetes, Addison’s disease); IB D3.3.4 (SL) type 1 and type 2 diabetes

When the endocrine system secretes too much (hyper-) or too little (hypo-) of a hormone, a disorder results. NEET lists seven to know in brief; IB asks only about diabetes, in more depth. For more on these conditions, see the MedlinePlus overview of endocrine diseases.

Endocrine system disorders for NEET at a glance

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Diabetes mellitus: the commonest endocrine system disorder

Diabetes mellitus is prolonged hyperglycaemia caused by too little insulin or by cells failing to respond to it. Without insulin action, cells take up little glucose, the liver keeps releasing glucose, and fat and protein are broken down for energy.

• Glycosuria: blood glucose rises above the renal threshold (about 180 mg dL⁻¹), so the kidney cannot reabsorb all the filtered glucose and it appears in the urine.
• Polyuria and thirst: glucose in the filtrate holds water by osmosis, so a large volume of urine is produced and the person is always thirsty.
• Ketone bodies: fat is broken down so fast that the liver makes ketone bodies (e.g. acetoacetic acid, acetone). They make the blood acidic (ketoacidosis), especially in type 1, and can be life-threatening (NCERT: ‘harmful compounds known as ketone bodies’).
• Weight loss, tiredness and, in the long term, damage to blood vessels, eyes, kidneys and nerves.

Read more in the NIDDK (US National Institutes of Health) guide to diabetes.

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11 Common doubts about hormones and the endocrine system

These are the doubts students raise most often about the human endocrine system, with short answers.

If hormones reach every cell in the body, why do only some cells respond?

Only target cells have the right receptor. Insulin can only affect a cell with insulin receptors, just as a radio signal is only heard by a radio tuned to that station. This is also why one hormone can have different effects in different tissues: the receptors and the pathways behind them differ. It is how the endocrine system can broadcast to the whole body yet act selectively.

Why is the pituitary called the master gland if the hypothalamus controls it?

Because its trophic hormones (TSH, ACTH, FSH, LH) control the thyroid, adrenal cortex and gonads. But the pituitary is itself under the command of the hypothalamus through releasing and inhibiting hormones, and of feedback from its target glands. ‘Master gland’ is a traditional name; the hypothalamus is really the boss of the endocrine system.

Are oxytocin and ADH pituitary hormones or hypothalamic hormones?

Both answers appear in books. They are made by neurosecretory cells in the hypothalamus and released from the posterior pituitary. In an MCQ that asks which hormones are ‘released from’ or ‘stored in’ the posterior pituitary, the answer is oxytocin and ADH; if it asks where they are synthesised, the answer is the hypothalamus.

Glucose, glycogen, glucagon: which is which?

Glucose is the sugar in the blood. Glycogen is the polysaccharide store of glucose in liver and muscle. Glucagon is the hormone from α cells that tells the liver to break glycogen down. A useful trick: glucagon is what you need when glucose is gone.

If type 2 diabetics make insulin, why do some of them need insulin injections?

In type 2 diabetes the cells are resistant, so more insulin is needed for the same effect. At first the β cells make extra, but over years they often wear out and secretion falls. When diet, exercise and tablets can no longer keep blood glucose down, extra insulin overcomes the resistance. The MedlinePlus diabetes page explains the treatment options.

Why does diabetes make you pass so much urine and feel thirsty?

When blood glucose goes above the renal threshold (about 180 mg dL⁻¹), the kidney tubules cannot reabsorb all the filtered glucose. The glucose left in the filtrate holds water by osmosis, so much more urine is produced (polyuria). The body loses water and the person feels very thirsty.

Is adrenaline a hormone or a neurotransmitter?

Adrenaline (epinephrine) secreted by the adrenal medulla into the blood is a hormone. Its close relative noradrenaline is mainly the neurotransmitter of sympathetic nerve endings, and is also secreted in small amounts as a hormone. The same kind of chemical can be a hormone or a neurotransmitter depending on how it is delivered: through the blood or across a synapse. The nervous system and the endocrine system share several of these chemicals.

Why does a lack of iodine make the thyroid bigger, when it makes less hormone?

The thyroid needs iodine to make T3 and T4. With too little iodine, hormone levels fall, so the hypothalamus and pituitary get less negative feedback and secrete more TRH and TSH. TSH keeps stimulating the thyroid to grow and work harder, and it enlarges into a goitre, but without iodine it still cannot make enough hormone. It is a neat example of endocrine system feedback going wrong.

Why does homeostasis rely on negative rather than positive feedback?

In the endocrine system, negative feedback opposes any change, so it brings a variable back towards its set point whether it has risen or fallen. Positive feedback reinforces a change, so the variable would keep moving away from the set point. That is useful only for events that must finish quickly, such as childbirth or ovulation.

Can hormones be taken as tablets if they are ‘non-nutrient’?

Yes, many can. ‘Non-nutrient’ only means the hormones of the endocrine system are not used for energy or building material. Steroid and thyroid hormones survive digestion and are absorbed, so thyroxine, cortisol-type drugs and contraceptive pills work by mouth. Protein hormones such as insulin are digested by proteases in the gut, which is why insulin has to be injected.

12 Key terms

Many one-mark questions on the endocrine system test a definition.

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13 FAQ

Short answers to the questions we are asked most about hormones and the endocrine system.

14 Quick check

Tap each question to check what you know about the human endocrine system.