Chemical Coordination and Integration

(a) Exocrine gland:
Exocrine glands are glands that pour their secretions into a duct (duct glands). These ducts open either onto a body surface or into a body cavity. Examples: salivary glands, sweat glands, liver (bile secretion), pancreas (exocrine part secreting digestive enzymes).

(b) Endocrine gland:
Endocrine glands are ductless glands that secrete their products (hormones) directly into the blood (or lymph). Because they lack ducts, they are also called ductless glands. Examples: pituitary gland, thyroid gland, adrenal gland, pancreas (islets of Langerhans).

(c) Hormone:
Hormones are non-nutrient chemical messengers produced in trace amounts by specialised tissues (endocrine glands or cells). They are secreted directly into the blood and are transported to distant target organs/tissues where they produce specific physiological effects. They act as intercellular messengers and are generally inactivated after their action. Examples: insulin, thyroxine, adrenaline.

Given: We are required to show the location of endocrine glands in the human body diagrammatically.

Answer:
Draw a simple outline of the human body and label the following endocrine glands at their correct anatomical positions:

1. Hypothalamus — base of the brain (diencephalon region)
2. Pituitary gland (Hypophysis) — below the hypothalamus, in the sella turcica of the sphenoid bone
3. Pineal gland — dorsal side of the forebrain
4. Thyroid gland — in the neck, on either side of the trachea
5. Parathyroid glands — four in number, on the posterior surface of the thyroid gland
6. Thymus — between the lungs, behind the sternum (in the thoracic cavity)
7. Adrenal glands — one on top of each kidney (suprarenal glands)
8. Pancreas (Islets of Langerhans) — in the abdomen, behind the stomach
9. Gonads:
- Testis — in the scrotal sac (males)
- Ovary — in the pelvic cavity (females)
10. Heart (Atrium) — produces Atrial Natriuretic Factor (ANF)
11. Kidney — produces erythropoietin

*(Note: In the board exam, draw a neat labelled diagram of the human torso showing all the above glands at their respective positions.)*

(a) Hypothalamus:
The hypothalamus produces releasing and inhibiting hormones (neurohormones):
- Gonadotrophin Releasing Hormone (GnRH)
- Thyrotrophin Releasing Hormone (TRH)
- Corticotrophin Releasing Hormone (CRH)
- Growth Hormone Releasing Hormone (GHRH)
- Growth Hormone Inhibiting Hormone (GHIH / Somatostatin)
- Prolactin Releasing Hormone (PRH)
- Prolactin Inhibiting Hormone (PIH)

(b) Pituitary:
- *Pars distalis (Anterior pituitary):* Growth Hormone (GH), Prolactin (PRL), Thyroid Stimulating Hormone (TSH), Adrenocorticotrophic Hormone (ACTH), Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH)
- *Pars intermedia:* Melanocyte Stimulating Hormone (MSH)
- *Pars nervosa (Posterior pituitary):* Oxytocin, Vasopressin (ADH — Anti-Diuretic Hormone)

(c) Thyroid:
- Thyroxine (T₄)
- Triiodothyronine (T₃)
- Thyrocalcitonin (TCT)

(d) Parathyroid:
- Parathyroid Hormone (PTH) / Parathormone

(e) Adrenal:
- *Adrenal medulla:* Epinephrine (Adrenaline), Norepinephrine (Noradrenaline)
- *Adrenal cortex:*
- Glucocorticoids (e.g., Cortisol)
- Mineralocorticoids (e.g., Aldosterone)
- Androgens (small amounts)

(f) Pancreas:
- Glucagon (from α-cells of Islets of Langerhans)
- Insulin (from β-cells of Islets of Langerhans)
- Somatostatin (from δ-cells)

(g) Testis:
- Androgens (mainly Testosterone)
- Inhibin

(h) Ovary:
- Estrogens (mainly Estradiol)
- Progesterone
- Relaxin (during pregnancy)

(i) Thymus:
- Thymosins (e.g., Thymosin α₁, Thymosin β₄)

(j) Atrium (Heart):
- Atrial Natriuretic Factor (ANF)

(k) Kidney:
- Erythropoietin

(l) G-I Tract (Gastrointestinal Tract):
- Gastrin
- Secretin
- Cholecystokinin (CCK)
- Gastric Inhibitory Peptide (GIP)

| Hormones | Target gland |
|---|---|
| (a) Hypothalamic hormones | Pituitary gland |
| (b) Thyrotrophin (TSH) | Thyroid gland |
| (c) Corticotrophin (ACTH) | Adrenal cortex |
| (d) Gonadotrophins (LH, FSH) | Gonads (Testis and Ovary) |
| (e) Melanotrophin (MSH) | Melanocytes (pigment cells) in the skin |

Explanation:
- Hypothalamic hormones (releasing/inhibiting hormones) act on the anterior pituitary to regulate its secretions.
- TSH stimulates the thyroid gland to produce thyroxine (T₃ and T₄).
- ACTH stimulates the adrenal cortex to secrete glucocorticoids and mineralocorticoids.
- LH and FSH act on the gonads to regulate gametogenesis and sex hormone production.
- MSH acts on melanocytes in the skin to regulate pigmentation.

(a) Parathyroid Hormone (PTH):
- Secreted by the parathyroid glands (chief cells).
- It is a hypercalcemic hormone — it increases blood $\text{Ca}^{2+}$ levels.
- Functions:
1. Stimulates bone resorption (demineralisation of bone), releasing $\text{Ca}^{2+}$ into blood.
2. Stimulates reabsorption of $\text{Ca}^{2+}$ from renal tubules, reducing its loss in urine.
3. Stimulates absorption of $\text{Ca}^{2+}$ from the intestine (by activating Vitamin D).
4. Plays a major role in calcium homeostasis in the body.

(b) Thyroid Hormones (T₃ and T₄):
- Secreted by the follicular cells of the thyroid gland.
- Functions:
1. Regulate the Basal Metabolic Rate (BMR).
2. Stimulate synthesis of proteins and control metabolism of carbohydrates, proteins and fats.
3. Essential for normal development and maturation of the Central Nervous System (CNS).
4. Promote erythropoiesis (RBC formation).
5. Regulate the menstrual cycle in females.
6. Influence water and electrolyte balance.
7. Maintain body temperature.
- Thyrocalcitonin (TCT): Decreases blood $\text{Ca}^{2+}$ levels (hypocalcemic effect) by inhibiting bone resorption.

(c) Thymosins:
- Secreted by the thymus gland.
- Functions:
1. Play a major role in the differentiation of T-lymphocytes (T-cells), which provide cell-mediated immunity.
2. Promote production of antibodies by B-lymphocytes, thereby providing humoral immunity.
3. The thymus is most active during childhood; it degenerates by middle age, reducing thymosin production and thereby reducing immune responses in old age.

(d) Androgens:
- Secreted mainly by the Leydig cells (interstitial cells) of the testis; small amounts also from adrenal cortex.
- Main androgen: Testosterone.
- Functions:
1. Stimulate development, maturation and functioning of male accessory sex organs (epididymis, vas deferens, seminal vesicles, prostate).
2. Stimulate appearance of male secondary sex characters (beard, moustache, deep voice, broad shoulders, etc.).
3. Stimulate spermatogenesis (sperm production).
4. Influence male sexual behaviour (libido).
5. Promote anabolic pathways (protein synthesis, muscle development).
6. Stimulate erythropoiesis.

(e) Estrogens:
- Secreted by the Graafian follicles of the ovary; also by the corpus luteum and placenta.
- Functions:
1. Stimulate growth and development of female accessory sex organs (uterus, fallopian tubes, vagina).
2. Stimulate appearance of female secondary sex characters (development of breasts, feminine body contour, high-pitched voice, etc.).
3. Regulate the menstrual cycle.
4. Stimulate growth of mammary glands.
5. Influence female sexual behaviour.
6. Promote oogenesis and follicular development.

(f) Insulin and Glucagon:

Insulin:
- Secreted by β-cells (Beta cells) of the Islets of Langerhans in the pancreas.
- It is a hypoglycemic hormone — it lowers blood glucose levels.
- Functions:
1. Stimulates cellular uptake and utilisation of glucose by body cells.
2. Promotes glycogenesis (conversion of glucose to glycogen for storage in liver and muscles).
3. Promotes synthesis of proteins and fats.
4. Inhibits glycogenolysis and gluconeogenesis.
- Deficiency of insulin or insulin resistance leads to Diabetes mellitus, characterised by hyperglycemia and glycosuria.

Glucagon:
- Secreted by α-cells (Alpha cells) of the Islets of Langerhans.
- It is a hyperglycemic hormone — it raises blood glucose levels.
- Functions:
1. Stimulates glycogenolysis (breakdown of glycogen to glucose) in the liver.
2. Stimulates gluconeogenesis (synthesis of glucose from non-carbohydrate sources).
3. Reduces cellular glucose uptake and utilisation.
4. Acts as an emergency hormone to maintain blood glucose during fasting/starvation.

(a) Hyperglycemic hormone and Hypoglycemic hormone:
- Hyperglycemic hormone (raises blood glucose): Glucagon (secreted by α-cells of pancreas)
- Hypoglycemic hormone (lowers blood glucose): Insulin (secreted by β-cells of pancreas)

(b) Hypercalcemic hormone:
- Parathyroid Hormone (PTH) — secreted by the parathyroid glands; it increases blood $\text{Ca}^{2+}$ levels.

(c) Gonadotrophic hormones:
- Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) — both secreted by the pars distalis of the anterior pituitary gland. They act on the gonads (testis and ovary).

(d) Progestational hormone:
- Progesterone — secreted by the corpus luteum of the ovary (also by the placenta during pregnancy). It prepares the uterus for implantation and maintains pregnancy.

(e) Blood pressure lowering hormone:
- Atrial Natriuretic Factor (ANF) — secreted by the atrial wall of the heart. It causes vasodilation and promotes sodium and water excretion, thereby decreasing blood pressure.

(f) Androgens and Estrogens:
- Androgens: Testosterone (secreted by Leydig cells of testis); also small amounts from adrenal cortex.
- Estrogens: Estradiol (secreted by Graafian follicles of ovary); also from corpus luteum and placenta.

(a) Diabetes mellitus:
- Hormonal deficiency: Deficiency of Insulin (secreted by β-cells of Islets of Langerhans of pancreas) and/or insulin resistance.
- Explanation: Insulin is required for cellular uptake and utilisation of glucose and for glycogenesis. Its deficiency leads to hyperglycemia (high blood glucose), glycosuria (glucose in urine), polyuria, polydipsia and polyphagia — collectively called Diabetes mellitus.

(b) Goitre:
- Hormonal deficiency: Deficiency of Thyroid hormones (T₃ and T₄), usually due to deficiency of iodine in the diet.
- Explanation: When iodine is deficient, the thyroid gland cannot synthesise adequate thyroxine. Low thyroxine levels stimulate the pituitary to secrete more TSH (due to loss of negative feedback). Excess TSH causes abnormal enlargement of the thyroid gland, resulting in a swelling in the neck called Goitre (Simple/Endemic goitre).

(c) Cretinism:
- Hormonal deficiency: Deficiency of Thyroid hormones (T₃ and T₄) during foetal life or early childhood (congenital hypothyroidism).
- Explanation: Thyroid hormones are essential for the normal development and maturation of the central nervous system. Their deficiency in early life leads to Cretinism, characterised by stunted growth (dwarfism), mental retardation, low intelligence, delayed sexual maturity, abnormal skin, and deaf-mutism.

Given: Mechanism of action of FSH (Follicle Stimulating Hormone).

FSH is a protein/peptide hormone, so it cannot enter the target cell directly. It acts through a second messenger mechanism (membrane receptor-mediated action).

Mechanism:

Step 1 — Hormone-Receptor Binding:
FSH (first messenger) is released from the anterior pituitary and reaches the target cells (gonadal cells — Sertoli cells in testis; granulosa cells in ovary) via blood. It binds to specific protein receptors located on the cell membrane (plasma membrane) of the target cell.

Step 2 — Activation of Adenylyl Cyclase:
The hormone-receptor complex activates a G-protein on the inner surface of the membrane, which in turn activates the enzyme adenylyl cyclase (adenylate cyclase).

Step 3 — Formation of Second Messenger (cAMP):
Adenylyl cyclase catalyses the conversion of ATP to cyclic AMP (cAMP), which acts as the second messenger inside the cell.
$$\text{ATP} \xrightarrow{\text{Adenylyl cyclase}} \text{cAMP} + \text{PP}_i$$

Step 4 — Activation of Protein Kinases:
cAMP activates intracellular enzymes called protein kinases, which phosphorylate specific proteins.

Step 5 — Physiological Response:
The activated proteins bring about the specific physiological response:
- In females: FSH stimulates growth and development of ovarian follicles and secretion of estrogens.
- In males: FSH stimulates Sertoli cells and promotes spermatogenesis.

Step 6 — Inactivation:
cAMP is inactivated by the enzyme phosphodiesterase, terminating the hormonal response.

Summary: FSH → binds to membrane receptor → activates adenylyl cyclase → cAMP (second messenger) → protein kinase activation → physiological response.

Matching:

| Column I | Column II |
|---|---|
| (a) T₄ (Thyroxine) | (ii) Thyroid |
| (b) PTH (Parathyroid Hormone) | (iv) Parathyroid |
| (c) GnRH (Gonadotrophin Releasing Hormone) | (i) Hypothalamus |
| (d) LH (Luteinising Hormone) | (iii) Pituitary |

Justification:
- T₄ (Thyroxine): Secreted by the follicular cells of the thyroid gland.
- PTH (Parathyroid Hormone / Parathormone): Secreted by the chief cells of the parathyroid glands.
- GnRH (Gonadotrophin Releasing Hormone): Secreted by neurosecretory cells of the hypothalamus; it stimulates the pituitary to release LH and FSH.
- LH (Luteinising Hormone): Secreted by the pars distalis of the anterior pituitary gland; it acts on the gonads.