Chapter 5.6: Chemical Coordination and Integration

1. Human Endocrine System

The endocrine system provides chemical coordination through hormones. Endocrine glands are ductless glands that release their secretions (hormones) directly into the bloodstream.

• Hormones: Non-nutrient chemicals which act as intercellular messengers and are produced in trace amounts.

a) The Hypothalamus

• Location: Located at the basal part of the diencephalon (forebrain).
• Role: It is the master control centre of the endocrine system. It contains several groups of neurosecretory cells called nuclei which produce hormones. These hormones regulate the synthesis and secretion of pituitary hormones.
• Hormones of the Hypothalamus:
  • Releasing Hormones: Stimulate the secretion of pituitary hormones. Example: Gonadotrophin releasing hormone (GnRH) stimulates the pituitary to release gonadotrophins.
  • Inhibiting Hormones: Inhibit the secretion of pituitary hormones. Example: Somatostatin inhibits the release of growth hormone from the pituitary.
• Connection to Pituitary: These hormones reach the pituitary gland through a portal circulatory system and regulate the functions of the anterior pituitary. The posterior pituitary is under the direct neural regulation of the hypothalamus.

b) The Pituitary Gland

• Location: Located in a bony cavity called sella turcica and is attached to the hypothalamus by a stalk.
• Lobes of the Pituitary:
  • Adenohypophysis (Anterior Pituitary): Produces and secretes several important hormones.
  • Neurohypophysis (Posterior Pituitary): Stores and releases two hormones which are actually synthesised by the hypothalamus and are transported axonally to the neurohypophysis.

Hormones of the Anterior Pituitary

1. Growth Hormone (GH):
   • Function: Regulates the growth of the body by promoting protein synthesis and growth of bones and muscles.
   • Disorders:
     • Hyposecretion (Dwarfism): Stunted growth.
     • Hypersecretion (Gigantism): Abnormal growth of the body. Acromegaly is a condition of hypersecretion in adults, characterized by the enlargement of the jaw, hands, and feet.
2. Prolactin (PRL):
   • Function: Regulates the growth of the mammary glands and formation of milk in them.
3. Thyroid Stimulating Hormone (TSH):
   • Function: Stimulates the synthesis and secretion of thyroid hormones from the thyroid gland.
4. Adrenocorticotrophic Hormone (ACTH):
   • Function: Stimulates the synthesis and secretion of steroid hormones called glucocorticoids from the adrenal cortex.
5. Luteinizing Hormone (LH):
   • Function: In males, it stimulates the synthesis and secretion of hormones called androgens from the testis. In females, it induces ovulation of fully mature follicles (Graafian follicles) and maintains the corpus luteum.
6. Follicle Stimulating Hormone (FSH):
   • Function: In males, FSH and androgens regulate spermatogenesis. In females, FSH stimulates the growth and development of the ovarian follicles.

Hormones of the Posterior Pituitary

1. Oxytocin:
   • Function: Stimulates a vigorous contraction of the uterus at the time of childbirth, and milk ejection from the mammary gland.
2. Antidiuretic Hormone (ADH) or Vasopressin:
   • Function: Stimulates reabsorption of water and electrolytes by the distal tubules and thereby reduces loss of water through urine (diuresis).
   • Disorders:
     • Hyposecretion (Diabetes Insipidus): Characterized by diminished ability of the kidney to conserve water leading to water loss and dehydration.

Feedback Control of Tropic Hormones

• The secretion of hormones from the anterior pituitary is controlled by the hormones of the hypothalamus. This is further regulated by a feedback mechanism. For example, high levels of thyroid hormone in the blood inhibit the secretion of TSH from the pituitary and TRH from the hypothalamus. This is a negative feedback mechanism.

c) The Pineal Gland

• Location: Located on the dorsal side of the forebrain.
• Hormone: Secretes a hormone called melatonin.
• Function: Melatonin plays a very important role in the regulation of a 24-hour (diurnal) rhythm of our body. For example, it helps in maintaining the normal rhythms of the sleep-wake cycle, body temperature. In addition, melatonin also influences metabolism, pigmentation, the menstrual cycle as well as our defense capability.

d) The Thyroid Gland

• Location: Composed of two lobes which are located on either side of the trachea. Both the lobes are interconnected with a thin flap of connective tissue called the isthmus.
• Hormones:
  1. Thyroxine (T4) and Triiodothyronine (T3):
     • Function: Regulate the basal metabolic rate (BMR), support the process of red blood cell formation, control the metabolism of carbohydrates, proteins and fats, and maintain the water and electrolyte balance.
  2. Thyrocalcitonin (TCT):
     • Function: A protein hormone which regulates the blood calcium levels (lowers blood calcium).
• Disorders:
  • Hypothyroidism (Goiter): Enlargement of the thyroid gland due to a deficiency of iodine. In an adult woman, hypothyroidism may cause the menstrual cycle to become irregular. Cretinism is a condition of hypothyroidism in a pregnant woman which causes defective development and maturation of the growing baby leading to stunted growth, mental retardation, low intelligence quotient, abnormal skin, deaf-mutism, etc.
  • Hyperthyroidism (Grave’s Disease or Exophthalmic Goiter): An autoimmune disease where the body produces antibodies that mimic the action of TSH, leading to an enlarged thyroid, increased secretion of thyroid hormones, increased metabolic rate, weight loss, and protrusion of the eyeballs (exophthalmos).

e) The Parathyroid Gland

• Location: Four parathyroid glands are present on the back side of the thyroid gland, one pair each in the two lobes of the thyroid gland.
• Hormone: Secrete a peptide hormone called parathyroid hormone (PTH).
• Function: PTH increases the Ca2+ levels in the blood (hypercalcemic hormone). It acts on bones and stimulates the process of bone resorption (dissolution/demineralisation). PTH also stimulates reabsorption of Ca2+ by the renal tubules and increases Ca2+ absorption from the digested food.

f) The Thymus

• Location: A lobular structure located between the lungs behind the sternum on the ventral side of the aorta.
• Hormone: Secretes the peptide hormones called thymosins.
• Function: Thymosins play a major role in the differentiation of T-lymphocytes, which provide cell-mediated immunity. In addition, thymosins also promote the production of antibodies to provide humoral immunity. Thymus is degenerated in old individuals resulting in a decreased production of thymosins. As a result, the immune responses of old persons become weak.

g) The Adrenal Gland

• Location: One pair of adrenal glands, one at the anterior part of each kidney.
• Parts of the Adrenal Gland:
  • Adrenal Medulla (Inner part):
    • Hormones: Secretes two hormones called adrenaline (epinephrine) and noradrenaline (norepinephrine), commonly called catecholamines.
    • Function: These are rapidly secreted in response to stress of any kind and during emergency situations and are called emergency hormones or hormones of Fight or Flight. These hormones increase alertness, pupillary dilation, piloerection (raising of hairs), sweating, increase the heartbeat, the strength of heart contraction and the rate of respiration.
  • Adrenal Cortex (Outer part):
    • Hormones:
      • Glucocorticoids (e.g., Cortisol): Involved in carbohydrate metabolism, stimulate gluconeogenesis, lipolysis and proteolysis; and inhibit cellular uptake and utilisation of amino acids. Cortisol is also involved in maintaining the cardiovascular system as well as the kidney functions. It produces anti-inflammatory reactions and suppresses the immune response.
      • Mineralocorticoids (e.g., Aldosterone): Regulate the balance of water and electrolytes in our body. Aldosterone acts mainly at the renal tubules and stimulates the reabsorption of Na+ and water and excretion of K+ and phosphate ions.
    • Disorders:
      • Hyposecretion (Addison's Disease): Underproduction of hormones by the adrenal cortex alters carbohydrate metabolism causing acute weakness and fatigue.

h) The Pancreas

• Location: A composite gland which acts as both an exocrine and endocrine gland, located in the loop of the duodenum.
• Endocrine Part (Islets of Langerhans):
  • α-cells secrete Glucagon.
  • β-cells secrete Insulin.
• Hormones and Functions:
  • Glucagon: A peptide hormone, and plays an important role in maintaining the normal blood glucose levels. Glucagon acts mainly on the liver cells (hepatocytes) and stimulates glycogenolysis resulting in an increased blood sugar (hyperglycemia).
  • Insulin: A peptide hormone, which plays a major role in the regulation of glucose homeostasis. Insulin acts mainly on hepatocytes and adipocytes (cells of adipose tissue), and enhances cellular glucose uptake and utilisation. As a result, there is a rapid movement of glucose from blood to hepatocytes and adipocytes resulting in decreased blood glucose levels (hypoglycemia).
• Disorders:
  • Diabetes Mellitus: A disorder caused due to prolonged hyperglycemia. It is associated with loss of glucose through urine and formation of harmful compounds known as ketone bodies. It is caused due to the hyposecretion of insulin.

i) The Gonads

• Testis (in males):
  • Location: Present in the scrotal sac (outside the abdomen).
  • Endocrine Function: The Leydig cells or interstitial cells, which are present in the intertubular spaces, produce a group of hormones called androgens, mainly testosterone.
  • Function: Androgens regulate the development, maturation and functions of the male accessory sex organs like epididymis, vas deferens, seminal vesicles, prostate gland, urethra etc. These hormones stimulate muscular growth, growth of facial and axillary hair, aggressiveness, low pitch of voice etc. Androgens play a major stimulatory role in the process of spermatogenesis (formation of spermatozoa).
• Ovary (in females):
  • Location: Located in the abdomen.
  • Hormones:
    • Estrogen: Synthesised and secreted mainly by the growing ovarian follicles. It is responsible for the development of female secondary sex organs, development of growing ovarian follicles, and appearance of female secondary sex characters (e.g., high pitch of voice, etc.), mammary gland development.
    • Progesterone: Secreted by the corpus luteum. Progesterone supports pregnancy. Progesterone also acts on the mammary glands and stimulates the formation of alveoli (sac-like structures which store milk) and milk secretion.

j) Hormones of the Gastrointestinal (GI) Tract

• Gastrin: Acts on the gastric glands and stimulates the secretion of hydrochloric acid and pepsinogen.
• Secretin: Acts on the exocrine pancreas and stimulates secretion of water and bicarbonate ions.
• Cholecystokinin (CCK): Acts on both the pancreas and gall bladder and stimulates the secretion of pancreatic enzymes and bile juice, respectively.
• Gastric Inhibitory Peptide (GIP): Inhibits gastric secretion and motility.

2. Mechanism of Hormone Action

Hormones produce their effects on target tissues by binding to specific proteins called hormone receptors located in the target cells only.

a) Mechanism of Peptide/Protein Hormone Action (e.g., via cAMP)

These hormones are not lipid-soluble and cannot enter the target cell. They bind to receptors on the surface of the cell membrane.

1. The hormone (e.g., FSH) binds to its specific receptor on the cell surface.
2. This binding leads to the generation of a second messenger (e.g., cyclic AMP or cAMP).
3. The second messenger in turn activates existing enzymes in the cytoplasm.
4. This leads to a cascade of biochemical reactions, which results in the specific physiological response.

b) Mechanism of Steroid Hormone Action

These hormones are lipid-soluble and can easily pass through the cell membrane to bind to intracellular receptors.

1. The steroid hormone (e.g., estrogen) enters the cytoplasm of the target cell.
2. It binds to a specific intracellular receptor, forming a hormone-receptor complex.
3. This complex enters the nucleus and binds to a specific regulatory site on the DNA.
4. The binding of the complex to DNA regulates the transcription of specific genes into mRNA.
5. The mRNA is then translated into a specific protein.
6. This protein brings about the physiological and developmental effects.