Endocrine Glands And Hormones

**Endocrine glands** are **ductless glands**; they secrete their products directly into the bloodstream, which transports them to distantly located target organs. Their secretions are called **hormones**.

The classical definition of a hormone describes it as a chemical produced by endocrine glands, released into blood, and acting on a distant target organ. A more current scientific definition describes hormones as **non-nutrient chemicals that act as intercellular messengers and are produced in trace amounts**. This definition includes a wider range of signaling molecules.

Invertebrates have simple endocrine systems with a few hormones. Vertebrates, especially humans, have a more complex endocrine system with a large number of hormones providing coordination. The human endocrine system is composed of various endocrine glands and hormone-producing cells located throughout the body.

Human Endocrine System

The human endocrine system comprises organized endocrine glands and dispersed hormone-producing tissues/cells. The main organised endocrine glands are the pituitary, pineal, thyroid, adrenal, pancreas, parathyroid, thymus, testes (in males), and ovaries (in females). Additionally, organs like the gastrointestinal tract, liver, kidneys, and heart also produce hormones.

Let's describe the structure and functions of the major endocrine glands and the hypothalamus.

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The Hypothalamus

The **hypothalamus** is the basal part of the diencephalon, located in the forebrain. It regulates a wide range of body functions and plays a crucial role in coordinating the endocrine system, especially the pituitary gland. It contains several groups of neurosecretory cells called nuclei, which produce hormones.

Hypothalamic hormones are of two types:

• **Releasing hormones:** Stimulate the synthesis and secretion of pituitary hormones. Example: Gonadotrophin releasing hormone (GnRH) stimulates the pituitary to release gonadotrophins (LH and FSH).
• **Inhibiting hormones:** Inhibit the secretion of pituitary hormones. Example: Somatostatin inhibits the release of growth hormone (GH) from the pituitary.

These hypothalamic hormones are produced by neurosecretory cells, pass through axons, and are released from nerve endings. Releasing and inhibiting hormones reach the anterior pituitary through a **portal circulatory system**. The posterior pituitary is under the direct **neural regulation** of the hypothalamus.

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The Pituitary Gland

The **pituitary gland** is located in a bony cavity called sella tursica and is attached to the hypothalamus by a stalk. It is divided into two main parts anatomically: adenohypophysis and neurohypophysis.

• **Adenohypophysis (Anterior Pituitary):** Consists of pars distalis and pars intermedia.
  • **Pars distalis (Anterior Pituitary):** Produces six hormones:
    • Growth hormone (GH): Stimulates body growth and development. Over-secretion causes gigantism (in childhood) or acromegaly (in adults, severe disfigurement). Low secretion causes pituitary dwarfism.
    • Prolactin (PRL): Regulates mammary gland growth and milk formation.
    • Thyroid stimulating hormone (TSH): Stimulates thyroid gland to synthesize and secrete thyroid hormones.
    • Adrenocorticotrophic hormone (ACTH): Stimulates adrenal cortex to synthesize and secrete glucocorticoids.
    • Luteinizing hormone (LH) and Follicle stimulating hormone (FSH): Called gonadotrophins, stimulate gonadal activity. In males, LH stimulates androgen secretion from testis; FSH and androgens regulate spermatogenesis. In females, LH induces ovulation and maintains corpus luteum; FSH stimulates ovarian follicle growth.
  • **Pars intermedia:** Secretes Melanocyte stimulating hormone (MSH), which acts on melanocytes to regulate skin pigmentation. In humans, pars intermedia is almost merged with pars distalis.
• **Neurohypophysis (Pars nervosa or Posterior Pituitary):** Stores and releases two hormones that are actually synthesised in the hypothalamus and transported here:
  • Oxytocin: Acts on smooth muscles, stimulates contraction (e.g., vigorous uterine contraction during childbirth, milk ejection from mammary glands).
  • Vasopressin (ADH - Antidiuretic Hormone): Acts mainly on kidneys, stimulates water and electrolyte reabsorption in distal tubules, reducing water loss in urine (prevents diuresis). Impaired ADH synthesis/release causes Diabetes Insipidus (excessive water loss).

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The Pineal Gland

The **pineal gland** is located on the dorsal side of the forebrain. It secretes the hormone **melatonin**. Melatonin plays a very important role in regulating the body's 24-hour (diurnal) rhythm, such as the sleep-wake cycle and body temperature. It also influences metabolism, pigmentation, the menstrual cycle, and defense capability.

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Thyroid Gland

The **thyroid gland** consists of two lobes located on either side of the trachea, connected by an isthmus (Figure 19.3a). It is composed of follicles and stromal tissues. Follicular cells synthesize two iodine-containing hormones: **tetraiodothyronine (thyroxine, T$_4$)** and **triiodothyronine (T$_3$)**. Iodine is essential for thyroid hormone synthesis.

Functions of thyroid hormones (T$_3$, T$_4$):

• Regulate basal metabolic rate (BMR).
• Support RBC formation.
• Control metabolism of carbohydrates, proteins, and fats.
• Influence water and electrolyte balance.
• Essential for development and maturation of the central neural system.

Disorders of the thyroid gland:

• **Hypothyroidism:** Low hormone secretion. Caused by iodine deficiency (leads to **goitre**, enlarged thyroid). Hypothyroidism during pregnancy causes defective development of the baby (cretinism, stunted growth, mental retardation, etc.). In adult women, can cause irregular menstrual cycles.
• **Hyperthyroidism:** Excess hormone secretion (e.g., due to thyroid cancer or nodules). Adversely affects physiology. **Exopthalmic goitre (Graves’ disease)** is a form of hyperthyroidism (enlarged thyroid, protruding eyeballs, increased BMR, weight loss).

Thyroid gland also secretes a protein hormone, **thyrocalcitonin (TCT)**, which regulates blood calcium levels by decreasing it (antagonistic to PTH).

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Parathyroid Gland

Humans have four **parathyroid glands** located on the back side of the thyroid gland (one pair on each lobe) (Figure 19.3b). They secrete a peptide hormone called **Parathyroid hormone (PTH)**. PTH secretion is regulated by blood calcium ion levels.

Functions of PTH:

• **Increases blood Ca$^{2+}$ levels** (hypercalcemic hormone).
• Stimulates **bone resorption** (dissolution/demineralisation of bone).
• Stimulates **reabsorption of Ca$^{2+}$** by renal tubules.
• Increases **Ca$^{2+}$ absorption** from digested food in the intestine.

PTH and TCT together play a significant role in maintaining **calcium balance** (homeostasis) in the body.

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Thymus

The **thymus gland** is a lobular structure located between the lungs behind the sternum, on the ventral side of the aorta. It plays a major role in the development of the **immune system**, particularly in immunity mediated by lymphocytes.

The thymus secretes peptide hormones called **thymosins**. Thymosins are crucial for the differentiation of **T-lymphocytes**, which are involved in **cell-mediated immunity**. They also promote the production of antibodies by B-lymphocytes, providing **humoral immunity**. The thymus gland degenerates in old individuals, leading to decreased thymosin production and weakened immune responses.

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Adrenal Gland

Humans have one pair of **adrenal glands**, located at the anterior part of each kidney (Figure 19.4a). Each adrenal gland is composed of two types of tissues: the centrally located **adrenal medulla** and the outer **adrenal cortex** (Figure 19.4b).

• **Adrenal Medulla:** Secretes two hormones, **adrenaline (epinephrine)** and **noradrenaline (norepinephrine)**, collectively called **catecholamines**. These are rapidly secreted in response to stress or emergency situations, known as **emergency hormones** or **hormones of Fight or Flight**.
  • Increase alertness, pupil dilation, piloerection (raising of hairs), sweating.
  • Increase heart beat, strength of heart contraction, and respiration rate.
  • Stimulate breakdown of glycogen (increasing blood glucose).
  • Stimulate breakdown of lipids and proteins.
• **Adrenal Cortex:** Divided into three layers: zona reticularis (inner), zona fasciculata (middle), and zona glomerulosa (outer). Secretes many hormones called **corticoids**.
  • **Glucocorticoids** (main one is cortisol): Involved in carbohydrate metabolism. Stimulate gluconeogenesis (glucose synthesis from non-carbohydrates), lipolysis (fat breakdown), proteolysis (protein breakdown). Inhibit cellular uptake/utilisation of amino acids. Maintain cardiovascular system, blood pressure, and GFR. Produce anti-inflammatory reactions and suppress immune response (used therapeutically). Stimulate RBC production.
  • **Mineralocorticoids** (main one is aldosterone): Regulate water and electrolyte balance (Na$^+$, K$^+$). Stimulate reabsorption of Na$^+$ and water and excretion of K$^+$ and phosphate ions in renal tubules. Help maintain electrolyte balance, body fluid volume, osmotic pressure, and blood pressure.
  • Small amounts of **androgenic steroids** are also secreted, contributing to growth of axial, pubic, and facial hair during puberty.

Underproduction of adrenal cortex hormones can lead to Addison's disease (acute weakness, fatigue, altered metabolism).

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Pancreas

The **pancreas** is a **composite gland**, acting as both exocrine (secreting digestive enzymes into ducts) and endocrine gland. The endocrine part consists of **Islets of Langerhans** (1-2% of pancreatic tissue). Islets of Langerhans contain two main types of cells:

• $\alpha$-cells: Secrete **glucagon**.
• $\beta$-cells: Secrete **insulin**.

These two hormones are peptide hormones and play a major role in regulating **glucose homeostasis** (maintaining normal blood glucose levels):

• **Glucagon:** **Increases blood glucose levels (hyperglycemia)**. Acts mainly on liver cells (hepatocytes), stimulating glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (synthesis of glucose from non-carbohydrates). Reduces cellular glucose uptake/utilisation.
• **Insulin:** **Decreases blood glucose levels (hypoglycemia)**. Acts mainly on hepatocytes and adipocytes, enhancing cellular glucose uptake and utilisation. Stimulates conversion of glucose to glycogen (glycogenesis) in target cells.

Thus, insulin and glucagon maintain blood glucose balance through antagonistic actions. Prolonged hyperglycemia (high blood sugar) can lead to **diabetes mellitus**, associated with glucose loss in urine and ketone body formation. Insulin therapy is used to treat diabetes.

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Testis

A pair of **testes** is present in the scrotal sac of males. Testis functions as a primary sex organ and an endocrine gland. It contains seminiferous tubules and stromal (interstitial) tissue. The **Leydig cells** (interstitial cells) in the interstitial spaces produce a group of hormones called **androgens**, mainly **testosterone**.

Functions of androgens:

• Regulate development, maturation, and functions of male accessory sex organs (epididymis, vas deferens, seminal vesicles, prostate, urethra).
• Stimulate male secondary sex characters (muscular growth, facial/axillary hair, aggressiveness, low voice pitch).
• Stimulate spermatogenesis (sperm formation).
• Influence male sexual behaviour (libido).
• Anabolic effects on protein and carbohydrate metabolism.
• Stimulate erythropoiesis (RBC formation).

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Ovary

A pair of **ovaries** is located in the abdomen of females. Ovary is the primary female sex organ, producing ovum (egg) and female sex hormones (estrogen and progesterone). Composed of ovarian follicles and stromal tissues. Growing ovarian follicles mainly synthesize and secrete **estrogen**. After ovulation, the ruptured follicle forms the corpus luteum, which mainly secretes **progesterone**.

Functions of estrogen:

• Stimulates growth/activities of female secondary sex organs and secondary sex characters (high voice pitch, mammary gland development).
• Regulates female sexual behaviour.
• Development of growing ovarian follicles.

Functions of progesterone:

• Supports pregnancy.
• Acts on mammary glands, stimulating alveoli formation and milk secretion (lactation).

Hormones Of Heart, Kidney And Gastrointestinal Tract

Besides organized endocrine glands, several other organs produce hormones:

• **Heart:** Atrial wall secretes **Atrial Natriuretic Factor (ANF)**, a peptide hormone that decreases blood pressure by causing vasodilation (dilation of blood vessels).
• **Kidney:** Juxtaglomerular cells (JGA) produce **erythropoietin**, a peptide hormone that stimulates erythropoiesis (formation of RBCs).
• **Gastro-intestinal tract (GIT):** Endocrine cells in different parts secrete peptide hormones regulating digestion:
  • **Gastrin:** Acts on gastric glands, stimulates secretion of HCl and pepsinogen.
  • **Secretin:** Acts on exocrine pancreas, stimulates secretion of water and bicarbonate ions.
  • **Cholecystokinin (CCK):** Acts on pancreas and gall bladder, stimulates secretion of pancreatic enzymes and bile juice.
  • **Gastric Inhibitory Peptide (GIP):** Inhibits gastric secretion and motility.

Other non-endocrine tissues secrete **growth factors** essential for tissue growth, repair, and regeneration.

Mechanism Of Hormone Action

Hormones exert effects on target tissues by binding to specific protein molecules called **hormone receptors**, located only in target tissues. This binding forms a hormone-receptor complex, triggering biochemical and physiological changes in the target tissue.

Types of hormone receptors:

• **Membrane-bound receptors:** Present on the cell membrane of target cells. Hormones binding to these (e.g., protein/peptide hormones, catecholamines) typically do not enter the cell but trigger the generation of **second messengers** inside the cell (e.g., cyclic AMP, IP$_3$, Ca$^{++}$), which then regulate cellular metabolism and functions.

• **Intracellular receptors:** Located inside the target cell (mostly nuclear receptors in the nucleus). Hormones binding to these (e.g., steroid hormones, iodothyronines/thyroid hormones) typically enter the cell, bind to receptors, and the hormone-receptor complex interacts with the genome (DNA) to regulate gene expression and chromosome function. This leads to cumulative biochemical actions resulting in physiological and developmental effects.

Hormones are chemically diverse: peptide/polypeptide/protein hormones (e.g., insulin, glucagon, pituitary hormones), steroids (e.g., cortisol, testosterone), iodothyronines (thyroid hormones), and amino-acid derivatives (e.g., epinephrine).

The timing and amount of hormone release are precisely regulated by **feedback mechanisms**, often negative feedback (e.g., high blood sugar stimulates insulin release, which lowers sugar; as sugar falls, insulin release is reduced).

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