Endocrinology BZO5T12

Syllabus topics (RTMNU)

• Definition and general account of endocrine axes in vertebrates (HPA, HPG, HPT, and HPS axes)
• Hormones – classification based on chemical nature, solubility, functions, and mechanism of hormone action
• Hypothalamo–pituitary portal system
• Hormones of the pituitary gland and related disorders
• Regulation of hormone secretion – feedback control and neural regulation

Definition and General Account of Endocrine Axes in Vertebrates

Endocrinology is the study of endocrine (ductless) glands and their secretions, the hormones. A hormone is a chemical messenger secreted in small amounts by specialised cells directly into the blood, which travels to distant target cells and regulates their activity (Bayliss and Starling coined the term in 1905).

An endocrine axis is a three-step chain: hypothalamus → anterior pituitary → peripheral gland, linked by releasing hormones, tropic hormones and feedback.

In each axis the final hormone feeds back to inhibit the hypothalamus and pituitary, keeping levels stable.

Hormones – Classification

1. Based on chemical nature:

1. Peptide and protein hormones: chains of amino acids – insulin, glucagon, GH, prolactin, ADH, oxytocin; glycoproteins – FSH, LH, TSH, hCG.
2. Amino-acid derivatives (amines): from tyrosine – adrenaline, noradrenaline, thyroxine; from tryptophan – melatonin.
3. Steroid hormones: from cholesterol – cortisol, aldosterone, testosterone, oestradiol, progesterone, calcitriol.
4. Eicosanoids: from arachidonic acid – prostaglandins (local hormones).

2. Based on solubility: Water-soluble (hydrophilic) – peptides and catecholamines; travel free in blood, cannot cross membranes, act on surface receptors, quick and short action. Lipid-soluble (lipophilic) – steroids and thyroid hormones; travel bound to carrier proteins, cross membranes, act on intracellular receptors, slow and long-lasting.

3. Based on function: tropic hormones (act on other glands, e.g. TSH, ACTH), metabolic (insulin, thyroxine), growth (GH), reproductive (LH, oestrogen), water–mineral balance (ADH, aldosterone, PTH), stress (cortisol, adrenaline).

4. Mechanism of hormone action:

1. Through cell-surface receptors (second messenger mechanism) – E.W. Sutherland (Nobel 1971):
   • cAMP pathway: hormone (first messenger) binds a G-protein-coupled receptor → G_s protein activates adenylate cyclase → ATP → cAMP (second messenger) → activates protein kinase A → phosphorylates enzymes → response (e.g. glucagon and adrenaline cause glycogen breakdown in liver).
   • IP₃–DAG–Ca²⁺ pathway: phospholipase C splits PIP₂ into IP₃ (releases Ca²⁺ from ER) and DAG (activates protein kinase C) – e.g. GnRH, TRH, oxytocin.
   • Receptor tyrosine kinase: e.g. insulin – receptor autophosphorylates and starts a kinase cascade.
   • JAK–STAT pathway: GH, prolactin.
2. Through intracellular receptors (gene activation): steroid or thyroid hormone enters the cell → binds receptor in cytoplasm/nucleus → hormone–receptor complex binds a hormone response element on DNA → transcription of mRNA → new proteins → response (hours).

Hypothalamo–Pituitary Portal System

The pituitary (hypophysis) hangs from the hypothalamus by the infundibulum. It has an anterior lobe (adenohypophysis: pars distalis, pars tuberalis, pars intermedia) and a posterior lobe (neurohypophysis: pars nervosa).

1. Portal system (to the anterior pituitary): The superior hypophyseal artery forms a primary capillary plexus in the median eminence; hypothalamic neurons release releasing/inhibiting hormones here; hypophyseal portal veins carry them to a secondary capillary plexus in the anterior pituitary. So tiny amounts reach target cells quickly without dilution in general circulation.
2. Hypothalamo-hypophyseal tract (to the posterior pituitary): Neurons of the supraoptic and paraventricular nuclei make ADH and oxytocin, which travel down their axons (stored in Herring bodies) and are released into blood in the posterior lobe (neurosecretion).

Hormones of the Pituitary Gland and Related Disorders

Total failure of the anterior pituitary is Simmonds' disease (panhypopituitarism); after severe bleeding at childbirth it is Sheehan's syndrome.

Regulation of Hormone Secretion – Feedback Control and Neural Regulation

1. Negative feedback (most common): rising hormone level inhibits its own secretion – long loop (target hormone → hypothalamus/pituitary, e.g. cortisol inhibits CRH and ACTH), short loop (pituitary hormone → hypothalamus), ultra-short loop (hypothalamic hormone on itself).
2. Positive feedback: hormone increases its own secretion until an event ends – oxytocin during labour; oestrogen-induced LH surge causing ovulation.
3. Metabolite (humoral) control: blood glucose controls insulin and glucagon; blood Ca²⁺ controls PTH and calcitonin.
4. Neural regulation: sympathetic nerves stimulate the adrenal medulla (adrenaline in emergencies); suckling reflex releases oxytocin and prolactin; the hypothalamus links the nervous and endocrine systems.
5. Rhythms: circadian (cortisol peak in early morning, melatonin at night), pulsatile (GnRH), seasonal.

Likely exam questions

1. (Long, 8 marks) Classify hormones on the basis of chemical nature and solubility, and explain the mechanisms of hormone action.
2. (Long, 8 marks) Describe the hypothalamo–pituitary portal system and give the hormones of the pituitary gland with their disorders.
3. (Short, 4 marks) Write a note on endocrine axes (HPA, HPG, HPT and HPS).
4. (Short, 4 marks) Explain the cAMP second messenger mechanism.
5. (Short, 4 marks) Explain feedback regulation of hormone secretion.

Syllabus topics (RTMNU)

• Thyroid and Parathyroid Glands – Structure, hormones, functions and disorders
• Adrenal Gland – Structure, hormones, functions and disorders
• Pancreas and Gastrointestinal Hormones – Structure, hormones, functions and disorders of the pancreas
• Gastrointestinal hormones (somatostatin, gastrin, and secretin)
• Endocrine Functions of Other Organs – Hormones of the heart, kidney, pineal gland, and thymus

Thyroid Gland – Structure, Hormones, Functions and Disorders

Structure: Butterfly-shaped gland in the neck with two lobes joined by an isthmus, in front of the trachea. It is made of many hollow follicles lined by cuboidal follicular cells and filled with colloid (thyroglobulin). Between follicles lie parafollicular (C) cells, which secrete calcitonin.

Hormones: Thyroxine (T₄) and triiodothyronine (T₃) (T₃ is more active; most T₄ is converted to T₃ in tissues by deiodinase), and calcitonin.

Synthesis of thyroid hormones: (1) iodide trapping by the sodium–iodide symporter; (2) oxidation of iodide to iodine by thyroid peroxidase; (3) iodination of tyrosine residues of thyroglobulin → MIT and DIT; (4) coupling: MIT + DIT = T₃, DIT + DIT = T₄; (5) storage in colloid; (6) under TSH, colloid is taken in by endocytosis, digested, and T₃/T₄ released.

Functions: raise basal metabolic rate and heat production (calorigenic); increase O₂ use, heart rate; promote growth and brain development; carbohydrate, fat and protein metabolism; metamorphosis of tadpoles. Calcitonin lowers blood Ca²⁺ by inhibiting osteoclasts.

Parathyroid Glands – Structure, Hormones, Functions and Disorders

Structure: Usually four small glands on the back of the thyroid. Cells: chief (principal) cells secrete parathormone; oxyphil cells have uncertain function.

Parathormone (PTH) – raises blood calcium: (1) bone – stimulates osteoclastic bone resorption (indirectly through osteoblasts); (2) kidney – increases Ca²⁺ reabsorption, increases phosphate excretion, activates vitamin D to calcitriol; (3) intestine – via calcitriol, increases Ca²⁺ absorption. PTH and calcitonin act opposite to each other.

Disorders: Hypoparathyroidism (e.g. after accidental removal in thyroid surgery) → low Ca²⁺ → tetany (muscle spasms; Chvostek's and Trousseau's signs). Hyperparathyroidism → high Ca²⁺ → weak bones (osteitis fibrosa cystica), kidney stones, muscle weakness.

Adrenal Gland – Structure, Hormones, Functions and Disorders

Paired, cap-like glands on top of the kidneys; two parts with different origins: cortex (mesoderm) and medulla (neural crest, ectoderm).

Disorders: Addison's disease (cortex failure) – weakness, low BP, low sugar, bronze skin; Cushing's syndrome (excess cortisol) – moon face, buffalo hump, obesity of trunk, high sugar; Conn's syndrome (excess aldosterone) – hypertension, low K⁺; adrenogenital syndrome (congenital adrenal hyperplasia) – excess androgens, masculinisation of females; phaeochromocytoma – tumour of medulla causing episodes of high BP.

Pancreas – Structure, Hormones, Functions and Disorders

The pancreas is a mixed gland: exocrine acini secrete digestive juice; endocrine islets of Langerhans (1–2% of the gland) secrete hormones.

1. α (alpha) cells – glucagon: raises blood glucose by glycogenolysis and gluconeogenesis in liver.
2. β (beta) cells (most numerous) – insulin: lowers blood glucose by increasing glucose uptake in muscle and fat (GLUT4), glycogenesis, fat and protein synthesis; inhibits gluconeogenesis.
3. δ (delta) cells – somatostatin: inhibits insulin and glucagon secretion locally.
4. PP (F) cells – pancreatic polypeptide.

Disorders: Diabetes mellitus (insulin deficiency or resistance – high blood sugar, glucose in urine; detailed in Unit IV); hyperinsulinism (e.g. insulin-secreting tumour, insulin overdose) → hypoglycaemia, sweating, confusion, coma.

Gastrointestinal Hormones (Somatostatin, Gastrin and Secretin)

Other gut hormones: cholecystokinin (CCK – gall bladder contraction, enzyme-rich pancreatic juice), GIP and GLP-1 (incretins, increase insulin), ghrelin (hunger).

Endocrine Functions of Other Organs – Heart, Kidney, Pineal Gland and Thymus

1. Heart: atrial wall cells secrete atrial natriuretic peptide (ANP) when atria are stretched by high blood volume; it causes loss of Na⁺ and water in urine, dilates blood vessels and lowers BP (opposite to aldosterone). Ventricles secrete BNP (marker of heart failure).
2. Kidney: erythropoietin (stimulates RBC formation when O₂ is low), renin (enzyme starting the renin–angiotensin–aldosterone system), and active vitamin D (calcitriol).
3. Pineal gland: in the brain; secretes melatonin (from tryptophan via serotonin) in darkness. Regulates sleep and circadian rhythm, seasonal breeding (inhibits gonads in some animals), skin lightening in amphibians.
4. Thymus: in the chest above the heart; secretes thymosins, thymopoietin and thymulin for maturation of T-lymphocytes; large in children, shrinks (involutes) after puberty.

Likely exam questions

1. (Long, 8 marks) Describe the structure of the thyroid gland, the synthesis and functions of thyroid hormones, and its disorders.
2. (Long, 8 marks) Describe the structure of the adrenal gland and give the hormones of the cortex and medulla with their functions and disorders.
3. (Short, 4 marks) Write the functions of parathormone.
4. (Short, 4 marks) Write a note on the islets of Langerhans.
5. (Short, 4 marks) Give the source and functions of gastrin, secretin and somatostatin.

Syllabus topics (RTMNU)

• Endocrine Role of Testes – Testosterone, androstenedione, and 5-dihydrotestosterone (DHT)
• Endocrine Role of Ovaries – Estrogen, progesterone, human chorionic gonadotropin (hCG), relaxin and prolactin
• Hormonal Regulation of Puberty and Adolescence
• Reproductive Anomalies – Congenital disorders (hypogonadism and cryptorchidism)
• MOET (superovulation, artificial insemination, and embryo transfer)

Endocrine Role of Testes – Testosterone, Androstenedione and Dihydrotestosterone (DHT)

The Leydig (interstitial) cells of the testis produce male sex hormones (androgens) from cholesterol under the control of LH. Pathway (simplified): cholesterol → pregnenolone → progesterone/DHEA → androstenedione → testosterone → (in target tissues) DHT or oestradiol.

1. Testosterone – the main androgen:
   • In the foetus: develops the Wolffian ducts into epididymis, vas deferens and seminal vesicles; helps descent of testes.
   • At puberty: growth of penis, scrotum and accessory glands; secondary sexual characters – beard, body hair, deep voice, muscle and bone growth, broad shoulders.
   • Maintains spermatogenesis (with FSH), libido and sexual behaviour, erythropoiesis; anabolic (protein-building) effect.
   • Negative feedback on GnRH and LH.
2. Androstenedione: a weak androgen produced by the testes and the adrenal cortex. It is mainly a precursor – converted to testosterone (by 17β-hydroxysteroid dehydrogenase) or to oestrone (by aromatase). In females it is the main androgen supplied to the ovary for oestrogen synthesis.
3. 5α-Dihydrotestosterone (DHT): formed from testosterone by 5α-reductase in target tissues (prostate, external genitalia, skin, hair follicles). It binds the androgen receptor more strongly than testosterone. Functions: development of the penis, scrotum and prostate in the foetus; prostate growth in adults; facial and body hair, acne, and male-pattern baldness. Deficiency of 5α-reductase causes ambiguous genitalia at birth; drugs blocking it (finasteride) treat prostate enlargement.

Sertoli cells also secrete inhibin (inhibits FSH) and, in the foetus, anti-Müllerian hormone.

Endocrine Role of Ovaries – Oestrogen, Progesterone, hCG, Relaxin and Prolactin

1. Oestrogens (oestradiol-17β – most potent; oestrone; oestriol in pregnancy): produced by granulosa cells of growing follicles (two-cell, two-gonadotropin model: theca cells make androgens under LH; granulosa cells convert them to oestrogen by aromatase under FSH). Functions: growth of uterus, vagina and breasts (duct system); proliferative phase of endometrium; female secondary sexual characters (broad pelvis, fat distribution); positive feedback causing the LH surge before ovulation; bone maintenance; closure of growth plates.
2. Progesterone – the "pregnancy hormone", from the corpus luteum (and later the placenta): converts endometrium to the secretory phase for implantation; maintains pregnancy; reduces uterine contractions; develops breast alveoli; thickens cervical mucus; raises basal body temperature slightly after ovulation; negative feedback on GnRH/LH.
3. Human chorionic gonadotropin (hCG): not ovarian – secreted by the syncytiotrophoblast of the embryo/placenta soon after implantation. Acts like LH: keeps the corpus luteum alive so that progesterone continues until the placenta takes over; peaks around 8–10 weeks. Detected in urine/blood in pregnancy tests; used in infertility treatment to trigger ovulation.
4. Relaxin: peptide from the corpus luteum (and placenta) in pregnancy; relaxes the pubic symphysis and pelvic ligaments, softens and dilates the cervix, helping childbirth; reduces uterine activity in early pregnancy.
5. Prolactin: from the anterior pituitary (not the ovary); with oestrogen and progesterone it develops the breasts in pregnancy, and after birth stimulates milk synthesis (lactation). High prolactin during breastfeeding suppresses GnRH, causing lactational amenorrhoea; in rodents it supports the corpus luteum.

Ovaries also secrete inhibin, small amounts of androgens and anti-Müllerian hormone.

Hormonal Regulation of Puberty and Adolescence

Puberty is the stage when reproductive organs mature and secondary sexual characters appear; adolescence is the wider period of physical, mental and social change (about 10–19 years).

1. Gonadarche: In childhood the GnRH pulse generator is suppressed. At puberty, increased kisspeptin signalling (and permissive signals like leptin from body fat) reactivates pulsatile GnRH, first at night → LH and FSH rise → gonads produce sex steroids.
2. Adrenarche: independent rise of adrenal androgens (DHEA) from about 6–8 years → pubic and axillary hair, body odour.
3. Growth hormone and IGF-1 rise together with sex steroids → growth spurt; oestrogen finally closes growth plates.
4. In boys (about 9–14 years): testis enlargement (first sign), penis growth, pubic and facial hair, voice deepening, muscle growth, spermarche.
5. In girls (about 8–13 years): breast development (thelarche – first sign), pubic hair (pubarche), growth spurt, widening of hips, menarche (first menstruation, usually 2–3 years after thelarche).
6. Puberty before 8 years in girls / 9 in boys is precocious puberty; absence by 13 in girls / 14 in boys is delayed puberty.

Reproductive Anomalies – Congenital Disorders (Hypogonadism and Cryptorchidism)

Hypogonadism means reduced function of the gonads (low sex hormones and/or gametes).

1. Primary (hypergonadotropic) hypogonadism: defect in the gonad itself, so LH and FSH are high. Examples: Klinefelter syndrome (47,XXY – small testes, infertility, breast enlargement), Turner syndrome (45,X – streak ovaries, short stature, no puberty), mumps orchitis.
2. Secondary (hypogonadotropic) hypogonadism: defect in hypothalamus or pituitary, so LH and FSH are low. Example: Kallmann syndrome – failure of GnRH neurons to migrate, with loss of smell (anosmia).
3. Treatment: hormone replacement (testosterone/oestrogen); gonadotropins or pulsatile GnRH for fertility in secondary type.

Cryptorchidism ("hidden testis") is failure of one or both testes to descend into the scrotum; it is the most common genital anomaly of newborn boys, especially premature babies. Descent is controlled by INSL3 (from Leydig cells) and testosterone. Effects: higher temperature damages spermatogenesis → infertility; higher risk of testicular cancer and torsion. Treatment: surgery (orchidopexy) in early childhood.

MOET (Superovulation, Artificial Insemination and Embryo Transfer)

MOET – Multiple Ovulation and Embryo Transfer is a technique for fast genetic improvement of livestock (especially cattle and buffalo), using reproductive hormones.

1. Selection: A genetically superior donor cow (high milk yield) and superior bull are selected.
2. Superovulation: The donor is given FSH (or PMSG/eCG) injections in decreasing doses for 4–5 days so that many follicles mature (6–8 or more eggs instead of one); prostaglandin F_2α is given to end the luteal phase and bring the cow into heat.
3. Artificial insemination: The donor is inseminated, usually two or three times at about 12-hour intervals, with frozen semen of the superior bull.
4. Embryo collection (flushing): About 7 days later, embryos (morula/blastocyst stage) are flushed out of the uterus non-surgically using a catheter.
5. Evaluation: Embryos are examined under a microscope and graded.
6. Embryo transfer: Good embryos are placed in the uterus of recipient (surrogate) cows whose oestrous cycles have been synchronised with the donor using hormones; extra embryos are frozen in liquid nitrogen.

Advantages: one superior cow can produce many calves in a year; rapid multiplication of elite and indigenous breeds (e.g. Gir, Sahiwal) under India's dairy development programmes; conservation of rare breeds; export of embryos instead of live animals; disease control.

Likely exam questions

1. (Long, 8 marks) Describe the endocrine role of the ovaries with reference to oestrogen, progesterone, hCG, relaxin and prolactin.
2. (Long, 8 marks) What is MOET? Describe superovulation, artificial insemination and embryo transfer and give its advantages.
3. (Short, 4 marks) Write the functions of testosterone and DHT.
4. (Short, 4 marks) Explain the hormonal regulation of puberty.
5. (Short, 4 marks) Write a note on cryptorchidism.

Syllabus topics (RTMNU)

• Endocrine regulation of growth, metabolism, reproduction, stress and water balance
• Endocrine disorders – diabetes mellitus, thyroid disorders, Addison’s disease, Cushing’s syndrome and obesity
• Behavioural endocrinology – endocrine control of stress, sleep and biological rhythms
• Recent advances and techniques – Xenohormones and endocrine disruptors
• Hormone therapy
• Hormone assays (RIA, CLIA, ELISA)

Endocrine Regulation of Growth, Metabolism, Reproduction, Stress and Water Balance

1. Growth: Growth hormone acts directly and through IGF-1 (from liver) to cause growth of bones (at epiphyseal plates) and muscles; thyroid hormones are needed for normal growth and brain development; insulin provides building material; sex steroids cause the pubertal growth spurt and later close growth plates.
2. Metabolism: Insulin (fed state – stores glucose, fat, protein) versus glucagon, cortisol, adrenaline and GH (fasting/stress – raise blood glucose). Thyroid hormones set the basal metabolic rate. Blood glucose is normally kept at about 70–100 mg/dL when fasting.
3. Reproduction: HPG axis – GnRH → FSH/LH → testosterone or oestrogen/progesterone; inhibin; placental hormones in pregnancy; prolactin and oxytocin in lactation.
4. Stress: Two systems – (a) sympatho-adrenomedullary system: quick release of adrenaline and noradrenaline ("fight or flight"); (b) HPA axis: CRH → ACTH → cortisol, which mobilises glucose, suppresses inflammation and helps long-term coping. Hans Selye's General Adaptation Syndrome: alarm reaction → resistance → exhaustion (chronic stress causes high BP, ulcers, low immunity).
5. Water and salt balance: ADH (from posterior pituitary when blood becomes concentrated) inserts aquaporin-2 water channels in kidney collecting ducts → water reabsorbed, concentrated urine. Aldosterone (via renin–angiotensin system when BP or Na⁺ falls) increases Na⁺ and water reabsorption. ANP from the heart does the opposite. Thirst is also controlled by the hypothalamus.

Endocrine Disorders – Diabetes Mellitus, Thyroid Disorders, Addison's Disease, Cushing's Syndrome and Obesity

1. Diabetes mellitus – a metabolic disorder with chronic high blood glucose (hyperglycaemia) due to lack of insulin, lack of insulin action, or both.

Symptoms: polyuria (frequent urination), polydipsia (thirst), polyphagia (hunger), weight loss, tiredness, slow wound healing. Diagnosis (standard criteria): fasting plasma glucose ≥126 mg/dL, 2-hour glucose ≥200 mg/dL in an oral glucose tolerance test, or HbA1c ≥6.5%. Complications: ketoacidosis (type 1), damage to eyes (retinopathy), kidneys (nephropathy), nerves (neuropathy), heart disease, diabetic foot. Gestational diabetes occurs in pregnancy. India has a very large number of diabetics.

2. Thyroid disorders: hypothyroidism (cretinism in children, myxoedema in adults, Hashimoto's thyroiditis), iodine-deficiency goitre, and hyperthyroidism (Graves' disease) – see Unit II. Diagnosis by blood T₃, T₄ and TSH; treated with levothyroxine (hypo) or anti-thyroid drugs, radioactive iodine or surgery (hyper).

3. Addison's disease (primary adrenal insufficiency): destruction of the adrenal cortex (often autoimmune, sometimes tuberculosis) → low cortisol and aldosterone. Symptoms: weakness, weight loss, low blood pressure, low blood sugar, salt craving, bronze pigmentation of skin (high ACTH/MSH). Treatment: replacement with hydrocortisone and fludrocortisone.

4. Cushing's syndrome: excess cortisol – from steroid medicines (most common), ACTH-secreting pituitary tumour (Cushing's disease) or adrenal tumour. Features: moon face, buffalo hump, central obesity with thin limbs, purple stretch marks, high blood sugar and BP, osteoporosis, weak muscles, low immunity.

5. Obesity: excess body fat harmful to health; WHO defines it as BMI ≥30 kg/m² (Indian guidelines use lower cut-offs for Asians, about ≥25). Endocrine links: leptin from fat signals fullness (obese people show leptin resistance); ghrelin from the stomach stimulates hunger; insulin resistance; cortisol excess; hypothyroidism; PCOS. Obesity increases risk of type 2 diabetes, heart disease and some cancers. Treatment: diet, exercise, behaviour change; drugs such as GLP-1 analogues; surgery in severe cases.

Behavioural Endocrinology – Endocrine Control of Stress, Sleep and Biological Rhythms

Behavioural endocrinology studies how hormones affect behaviour and how behaviour affects hormones.

1. Stress: CRH, ACTH, cortisol and adrenaline prepare the body to face threats; cortisol affects memory and mood (hippocampus, amygdala). Chronic stress keeps cortisol high → anxiety, depression, poor sleep, weight gain. Oxytocin reduces stress and promotes social bonding.
2. Sleep: Melatonin from the pineal rises in darkness and promotes sleep; cortisol peaks in the early morning to wake us; GH is released mainly during deep (slow-wave) sleep; orexin (hypocretin) from the hypothalamus keeps us awake (its loss causes narcolepsy). Lack of sleep raises ghrelin and lowers leptin, increasing appetite.
3. Biological rhythms:
   • Circadian (about 24 h) – sleep–wake cycle, body temperature, cortisol, melatonin. Master clock: suprachiasmatic nucleus (SCN) of the hypothalamus, reset by light through the retina (retinohypothalamic tract); it controls melatonin release from the pineal.
   • Ultradian (less than 24 h) – pulsatile GnRH and LH, sleep cycles.
   • Infradian (more than 24 h) – menstrual cycle (about 28 days).
   • Circannual/seasonal – breeding seasons, migration and hibernation, controlled by day length through melatonin.
4. Disturbed rhythms: jet lag, shift-work disorder – linked to metabolic and mood problems.

Recent Advances and Techniques – Xenohormones and Endocrine Disruptors

Xenohormones are substances from outside the body (synthetic or natural) that mimic or block natural hormones – e.g. xenoestrogens like bisphenol A (BPA, in plastics), phthalates, DDT, PCBs, some pesticides, and plant phytoestrogens (genistein in soy). Endocrine-disrupting chemicals (EDCs) interfere with hormone synthesis, transport, receptor binding or elimination.

Effects reported: falling sperm counts, early puberty, birth defects of genitalia (hypospadias, cryptorchidism), thyroid disorders, obesity and some hormone-related cancers; in wildlife – feminisation of male fish downstream of sewage, imposex in marine snails due to tributyltin (TBT), thin eggshells in birds due to DDT. Prevention: banning harmful chemicals, BPA-free products, safe pesticide use, avoiding heating food in plastic.

Hormone Therapy

1. Replacement therapy: insulin (recombinant human insulin) for diabetes, levothyroxine for hypothyroidism, hydrocortisone for Addison's disease, testosterone for male hypogonadism, GH for GH-deficient children, oestrogen–progesterone hormone replacement after menopause.
2. Contraception: combined oral pills, injectables, implants.
3. Infertility: FSH, hCG, GnRH analogues in IVF; MOET in animals.
4. Anti-hormone therapy in cancer: tamoxifen (blocks oestrogen receptors in breast cancer); GnRH analogues and anti-androgens in prostate cancer.
5. Anti-inflammatory use of corticosteroids (asthma, arthritis). Side-effects need medical supervision.

Hormone Assays (RIA, CLIA, ELISA)

Hormones are present in very small amounts (nanograms or picograms per mL), so sensitive immunoassays using antibodies are used.

Likely exam questions

1. (Long, 8 marks) Describe diabetes mellitus with reference to its types, symptoms, diagnosis and complications. Add a note on Cushing's syndrome.
2. (Long, 8 marks) Explain the principle and procedure of hormone assays – RIA, ELISA and CLIA.
3. (Short, 4 marks) Explain the endocrine control of water balance.
4. (Short, 4 marks) What are endocrine disruptors? Give examples and effects.
5. (Short, 4 marks) Write a note on circadian rhythm and melatonin.