The neural system provides rapid, point-to-point coordination, but its effects are short-lived and do not reach all cells. To achieve continuous and widespread regulation of cellular functions, a special kind of coordination is needed.

This function is carried out by hormones, which provide chemical integration. The neural system and the endocrine system work together, acting jointly to coordinate and regulate the physiological functions in the body in a synchronized manner.

Endocrine Glands And Hormones

Endocrine glands are also known as ductless glands because they lack ducts. Their secretions are released directly into the bloodstream or surrounding fluid.

The secretions of endocrine glands are called hormones.

Classical definition: Hormones are chemicals produced by endocrine glands, released into the blood, and transported to a distantly located target organ.

Current scientific definition: Hormones are non-nutrient chemicals that act as intercellular messengers and are produced in trace amounts. This broader definition includes various signaling molecules beyond those from traditional endocrine glands.

Invertebrates have relatively simple endocrine systems with few hormones. Vertebrates have a large number of chemicals that act as hormones, providing complex coordination.

Human Endocrine System

The human endocrine system is composed of organized endocrine glands and hormone-producing diffused tissues/cells located throughout the body. The major organized endocrine glands are (Figure 22.1):

• Pituitary gland
• Pineal gland
• Thyroid gland
• Adrenal glands
• Pancreas (endocrine part)
• Parathyroid glands
• Thymus
• Gonads (Testis in males, Ovary in females)

Besides these, other organs like the gastrointestinal tract, liver, kidney, and heart also produce hormones.

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The Hypothalamus

The hypothalamus is the basal part of the diencephalon (forebrain) (Figure 22.1 and 22.2). It is a neuroendocrine structure that regulates many body functions and controls the pituitary gland.

It contains several groups of neurosecretory cells called nuclei, which produce hypothalamic hormones.

Hypothalamic hormones regulate the synthesis and secretion of pituitary hormones. They are of two types:

• Releasing hormones: Stimulate the secretion of pituitary hormones (e.g., Gonadotrophin releasing hormone - GnRH, stimulates pituitary to synthesize and release gonadotrophins).
• Inhibiting hormones: Inhibit the secretion of pituitary hormones (e.g., Somatostatin inhibits release of growth hormone from pituitary).

These hormones are synthesized in hypothalamic neurons, transported down axons, and released from nerve endings. They reach the anterior pituitary via a portal circulatory system. The posterior pituitary is under the direct neural regulation of the hypothalamus; hypothalamic neurons synthesize oxytocin and vasopressin, which are stored and released by the posterior pituitary.

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The Pituitary Gland

Located in a bony cavity called sella tursica, attached to the hypothalamus by a stalk (Figure 22.2).

Anatomically divided into:

1. Adenohypophysis: Composed of:
   • Pars distalis (Anterior pituitary): Produces several hormones: Growth Hormone (GH), Prolactin (PRL), Thyroid Stimulating Hormone (TSH), Adrenocorticotrophic Hormone (ACTH), Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH). LH and FSH are collectively called gonadotrophins.
   • Pars intermedia: Secretes Melanocyte Stimulating Hormone (MSH). In humans, it is almost merged with pars distalis.
2. Neurohypophysis (Pars nervosa) (Posterior pituitary): Stores and releases two hormones synthesized by the hypothalamus: Oxytocin and Vasopressin (also called Anti-diuretic hormone - ADH).

Functions of Pituitary Hormones:

• GH (Growth Hormone): Stimulates body growth. Over-secretion in childhood causes gigantism; low secretion causes pituitary dwarfism. Excess secretion in adults causes acromegaly (disfigurement, especially face).
• PRL (Prolactin): Regulates growth of mammary glands and milk formation.
• TSH (Thyroid Stimulating Hormone): Stimulates thyroid gland to synthesize and secrete thyroid hormones.
• ACTH (Adrenocorticotrophic Hormone): Stimulates adrenal cortex to synthesize and secrete glucocorticoids.
• LH (Luteinizing Hormone):
  • Males: Stimulates testis (Leydig cells) to synthesize and secrete androgens.
  • Females: Induces ovulation of Graafian follicles and maintains corpus luteum.
• FSH (Follicle Stimulating Hormone):
  • Males: Along with androgens, regulates spermatogenesis.
  • Females: Stimulates growth and development of ovarian follicles.
• MSH (Melanocyte Stimulating Hormone): Acts on melanocytes to regulate skin pigmentation.
• Oxytocin: Acts on smooth muscles. Stimulates vigorous uterine contractions during childbirth and milk ejection from mammary glands.
• Vasopressin (ADH): Acts on kidney tubules (DCT, collecting duct), stimulating water and electrolyte reabsorption, reducing water loss in urine (anti-diuretic effect). Impairment leads to Diabetes Insipidus (excessive water loss, dehydration).

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The Pineal Gland

Located on the dorsal side of the forebrain. Secretes the hormone melatonin.

Function: Plays a key role in regulating the body's 24-hour (diurnal) rhythm (circadian rhythms). Helps maintain sleep-wake cycle, body temperature, influences metabolism, pigmentation, menstrual cycle, and defense capability.

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Thyroid Gland

Composed of two lobes located on either side of the trachea, connected by a thin tissue flap called the isthmus (Figure 22.3).

Structure: Composed of follicles (follicular cells enclosing a cavity) and stromal tissues.

Hormones synthesized by follicular cells: Tetraiodothyronine (Thyroxine, T$_4$) and Triiodothyronine (T$_3$). Iodine is essential for their synthesis.

Disorders:

• Hypothyroidism: Deficiency of thyroid hormones. Caused by iodine deficiency (leading to goitre - enlarged thyroid gland) or other reasons.
  • During pregnancy: Causes defective development of the baby (cretinism, mental retardation, etc.).
  • In adult women: Irregular menstrual cycles.
• Hyperthyroidism: Excess secretion of thyroid hormones. Caused by thyroid cancer or nodules. Adversely affects body physiology.
  • Exopthalmic goitre (Graves' disease): Form of hyperthyroidism with enlarged thyroid, protruding eyeballs, increased basal metabolic rate (BMR), weight loss.

Functions of Thyroid Hormones (T$_3$, T$_4$):

• Regulation of basal metabolic rate (BMR).
• Support formation of red blood cells.
• Control metabolism of carbohydrates, proteins, and fats.
• Influence maintenance of water and electrolyte balance.

Another hormone secreted by the thyroid gland (by parafollicular cells): Thyrocalcitonin (TCT). A protein hormone that regulates (decreases) blood calcium levels.

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Parathyroid Gland

In humans, four small parathyroid glands are present on the back side of the thyroid gland, one pair on each thyroid lobe (Figure 22.3 b).

Secretes a peptide hormone called Parathyroid Hormone (PTH). PTH secretion is regulated by circulating levels of calcium ions in the blood.

Function of PTH: Increases blood Ca$^{2+}$ levels (a hypercalcemic hormone). Acts on bones to stimulate bone resorption (release of Ca$^{2+}$ from bone), stimulates reabsorption of Ca$^{2+}$ by renal tubules, and increases Ca$^{2+}$ absorption from digested food in the intestine.

PTH, along with TCT (Thyrocalcitonin), plays a significant role in maintaining calcium balance (homeostasis) in the body.

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Thymus

A lobular gland located between the lungs, behind the sternum on the ventral side of the aorta. Plays a major role in the development of the immune system.

Secretes peptide hormones called thymosins.

Functions of Thymosins: Play a major role in the differentiation of T-lymphocytes (essential for cell-mediated immunity). Also promote the production of antibodies (providing humoral immunity).

The thymus gland degenerates in old individuals, leading to decreased thymosin production and weaker immune responses in the elderly.

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Adrenal Gland

Humans have a pair of adrenal glands, located on the anterior part of each kidney (Figure 22.4 a).

The adrenal gland is composed of two types of tissue (Figure 22.4 b):

• Adrenal Medulla: Central tissue.
• Adrenal Cortex: Outer tissue surrounding the medulla.

Hormones of Adrenal Medulla: Secretes two hormones collectively called catecholamines: Adrenaline (Epinephrine) and Noradrenaline (Norepinephrine). These are known as emergency hormones or hormones of "Fight or Flight" as they are secreted rapidly in response to stress or emergency situations.

Functions of Catecholamines: Increase alertness, pupillary dilation, piloerection (raising of hairs), sweating, heart rate, strength of heart contraction, rate of respiration. Stimulate breakdown of glycogen (increasing blood glucose), lipids, and proteins.

Hormones of Adrenal Cortex: Secretes many hormones called corticoids.

Adrenal cortex is divided into three layers: zona reticularis (inner), zona fasciculata (middle), and zona glomerulosa (outer).

Types of Corticoids:

• Glucocorticoids: Involved in carbohydrate metabolism. Cortisol is the main glucocorticoid.
• Mineralocorticoids: Regulate water and electrolyte balance. Aldosterone is the main mineralocorticoid.
• Small amounts of androgenic steroids are also secreted.

Functions of Corticoids:

• Glucocorticoids (Cortisol): Stimulate gluconeogenesis (glucose synthesis from non-carbohydrates), lipolysis (fat breakdown), proteolysis (protein breakdown). Inhibit cellular uptake and utilization of amino acids. Maintain cardiovascular system and kidney functions. Produce anti-inflammatory reactions and suppress immune response. Stimulate RBC production.
• Mineralocorticoids (Aldosterone): Act mainly on renal tubules, stimulating reabsorption of Na$^+$ and water, and excretion of K$^+$ and phosphate ions. Helps maintain electrolyte balance, body fluid volume, osmotic pressure, and blood pressure.
• Androgenic steroids: Play a role in growth of axial, pubic, and facial hair during puberty.

Adrenal cortex disorders: Underproduction of adrenal cortex hormones causes Addison's disease (weakness, fatigue, carbohydrate metabolism alteration).

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Pancreas

A composite gland, acting as both exocrine (secretes digestive enzymes) and endocrine gland. The endocrine part consists of clusters of cells called Islets of Langerhans (1-2 million islets, 1-2% of pancreatic tissue).

Cell types in Islets of Langerhans:

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

Function of Glucagon: Peptide hormone, plays an important role in maintaining normal blood glucose levels (hyperglycemia - increasing blood sugar). Acts mainly on liver cells (hepatocytes), stimulating glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (glucose synthesis from non-carbohydrates). Reduces cellular glucose uptake and utilization. Thus, glucagon is a hyperglycemic hormone.

Function of Insulin: Peptide hormone, plays a major role in regulating glucose homeostasis (hypoglycemia - decreasing blood sugar). Acts mainly on hepatocytes and adipocytes, enhancing cellular glucose uptake and utilization. Promotes rapid movement of glucose from blood into cells. Stimulates glycogenesis (conversion of glucose to glycogen) in target cells.

Glucose homeostasis is maintained by the balanced actions of insulin and glucagon.

Diabetes Mellitus: Complex disorder caused by prolonged hyperglycemia (high blood glucose). Results from insufficient insulin secretion and/or reduced sensitivity of target cells to insulin (insulin resistance). Associated with glucose loss in urine and formation of harmful ketone bodies. Treated with insulin therapy.

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Testis

A pair of testes in the scrotal sac of males (Figure 22.1). Functions as both a primary sex organ and an endocrine gland.

Structure: Composed of seminiferous tubules and stromal (interstitial) tissue. Leydig cells (interstitial cells) in intertubular spaces produce a group of steroid hormones called androgens, primarily testosterone.

Functions of Androgens (Testosterone):

• Regulate development, maturation, and functions of male accessory sex organs (epididymis, vas deferens, seminal vesicles, prostate gland, urethra).
• Stimulate muscular growth, growth of facial/axial hair, aggressiveness, deepening of voice (male secondary sex characters).
• Major stimulatory role in spermatogenesis (sperm formation).
• Influence male sexual behavior (libido) by acting on the CNS.
• Produce anabolic (synthetic) effects on protein and carbohydrate metabolism.
• Stimulate erythropoiesis (RBC formation).

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Ovary

A pair of ovaries in the abdomen of females (Figure 22.1). Functions as a primary female sex organ (produces ovum each menstrual cycle) and an endocrine gland.

Structure: Composed of ovarian follicles and stromal tissues. Produces two groups of steroid hormones: estrogen and progesterone.

• Estrogen: Synthesized and secreted mainly by the growing ovarian follicles.
• Progesterone: Secreted mainly by the corpus luteum, a structure formed from the ruptured follicle after ovulation.

Functions of Estrogen:

• Stimulate growth and activities of female secondary sex organs.
• Development of growing ovarian follicles.
• Appearance of female secondary sex characters (e.g., high pitch voice).
• Mammary gland development.
• Regulate female sexual behavior.

Function of Progesterone: Supports pregnancy. Also acts on mammary glands, stimulating formation of alveoli (milk storage structures) and milk secretion.

Hormones Of Heart, Kidney And Gastrointestinal Tract

Besides the organized endocrine glands, certain other tissues/organs also produce hormones:

• Heart: The atrial wall secretes a peptide hormone called Atrial Natriuretic Factor (ANF). Decreases blood pressure by causing vasodilation (dilation of blood vessels).
• Kidney: Juxtaglomerular cells produce a peptide hormone called Erythropoietin. Stimulates erythropoiesis (formation of RBCs) in the bone marrow.
• Gastro-intestinal Tract (GIT): Endocrine cells in different parts of the GIT secrete several peptide hormones that regulate digestive processes:
  • 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, respectively.
  • Gastric Inhibitory Peptide (GIP): Inhibits gastric secretion and motility.

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

Mechanism Of Hormone Action

Hormones exert their effects by binding to specific proteins called hormone receptors, located only in target tissues.

Types of hormone receptors:

• Membrane-bound receptors: Located on the cell membrane of target cells (for hormones that cannot easily cross the membrane).
• Intracellular receptors: Located inside the target cell, mostly nuclear receptors (present in the nucleus) (for hormones that can cross the membrane, e.g., steroid hormones, thyroid hormones).

Mechanism: Binding of a hormone to its specific receptor forms a hormone-receptor complex (Figure 22.5 a, b). Each receptor is specific to one hormone.

Chemical nature of hormones and their mechanism of action:

1. Peptide, Polypeptide, Protein hormones (e.g., insulin, glucagon, pituitary hormones, hypothalamic hormones): These are water-soluble and generally bind to membrane-bound receptors. They do not typically enter the target cell. Binding to the receptor generates second messengers inside the cell (e.g., cyclic AMP, IP$_3$, Ca$^{2+}$), which then trigger a cascade of intracellular events regulating cellular metabolism and physiological functions.
2. Steroids (e.g., cortisol, testosterone, estradiol, progesterone) and Iodothyronines (thyroid hormones): These are lipid-soluble and can cross the cell membrane to bind to intracellular receptors (often in the nucleus). The hormone-receptor complex interacts with the genome, regulating gene expression (transcription of specific genes) or chromosome function. This altered gene expression leads to the synthesis of new proteins and cumulative biochemical and physiological effects.
3. Amino-acid derivatives (e.g., epinephrine): Some act via membrane receptors (like protein hormones), while others may act intracellularly.

The hormone-receptor complex formation leads to specific biochemical changes in the target tissue, ultimately regulating its metabolism and physiological functions.

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