Chapter Notes

Chemical Coordination and Integration

Our bodies have two main systems for coordination and regulation: the neural system and the endocrine system. The neural system provides very fast, point-to-point communication, but its effects are short-lived. Since nerve fibres don't reach every single cell, another system is needed for continuous, widespread regulation. This is the job of the endocrine system, which uses chemical messengers called hormones. Together, the neural and endocrine systems coordinate all the physiological functions of the body.

Endocrine Glands and Hormones

Endocrine glands are unique because they do not have ducts to release their secretions. They are ductless glands. They release their chemical products, called hormones, directly into the bloodstream. The blood then transports these hormones to target organs throughout the body.

The scientific definition of a hormone has evolved. Today, we define them as: Hormones are non-nutrient chemicals that act as intercellular messengers and are produced in very small (trace) amounts.

This modern definition includes not only hormones from major endocrine glands but also molecules produced by other tissues. While invertebrates have simple endocrine systems, vertebrates, including humans, use a large number of hormones for coordination.

Human Endocrine System

The human endocrine system is made up of organized endocrine glands and various tissues or cells in different parts of the body that produce hormones.

The major endocrine glands are:

• Pituitary Gland
• Pineal Gland
• Thyroid Gland
• Adrenal Gland
• Pancreas
• Parathyroid Gland
• Thymus
• Gonads (Testis in males and Ovary in females)

In addition, organs like the gastrointestinal tract, liver, kidney, and heart also produce hormones.

The Hypothalamus

The hypothalamus is located at the base of the forebrain (diencephalon) and is a crucial link between the nervous and endocrine systems. It contains groups of nerve cells called neurosecretory cells (or nuclei) that produce hormones.

The primary role of the hypothalamus is to control the pituitary gland. It does this by producing two types of hormones:

1. Releasing Hormones: These stimulate the pituitary gland to secrete its hormones. [!example] Gonadotrophin releasing hormone (GnRH) from the hypothalamus tells the pituitary gland to synthesize and release gonadotrophins.
2. Inhibiting Hormones: These stop the pituitary gland from secreting its hormones. [!example] Somatostatin from the hypothalamus inhibits the release of growth hormone from the pituitary.

These hypothalamic hormones travel through nerve axons and are released at the nerve endings. They reach the anterior pituitary through a special portal circulatory system. The posterior pituitary, however, is under the direct neural control of the hypothalamus.

The Pituitary Gland

The pituitary gland is a small gland located in a bony cavity at the base of the skull called the sella tursica. It is connected to the hypothalamus by a stalk.

Anatomically, the pituitary is divided into two parts:

1. Adenohypophysis (Anterior Pituitary)
2. Neurohypophysis (Posterior Pituitary)

1. Adenohypophysis The adenohypophysis is further divided into two parts:

• Pars Distalis (Anterior Pituitary): This region produces several important hormones:
  • Growth Hormone (GH): Controls growth of the body.
  • Prolactin (PRL): Regulates the growth of mammary glands and milk formation.
  • Thyroid Stimulating Hormone (TSH): Stimulates the thyroid gland to produce thyroid hormones.
  • Adrenocorticotrophic Hormone (ACTH): Stimulates the adrenal cortex to produce glucocorticoids.
  • Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH): These are called gonadotrophins because they stimulate the gonads (testis and ovaries).
• Pars Intermedia: This region secretes only one hormone, Melanocyte Stimulating Hormone (MSH), which regulates skin pigmentation. In humans, the pars intermedia is almost merged with the pars distalis.

Disorders related to Growth Hormone (GH):

• Gigantism: Caused by over-secretion of GH in children, leading to abnormal body growth.
• Pituitary Dwarfism: Caused by low secretion of GH in children, resulting in stunted growth.
• Acromegaly: Caused by excess secretion of GH in adults, leading to severe disfigurement (especially of the face). It can cause serious complications and premature death if not treated.

Functions of Gonadotrophins (LH and FSH):

• In Males:
  • LH stimulates the testis to synthesize and secrete androgens (like testosterone).
  • FSH, along with androgens, regulates sperm formation (spermatogenesis).
• In Females:
  • LH triggers ovulation (release of the egg from the mature follicle) and maintains the corpus luteum (the structure formed from the ruptured follicle).
  • FSH stimulates the growth and development of ovarian follicles.

2. Neurohypophysis The neurohypophysis, also known as the pars nervosa or posterior pituitary, does not produce hormones. It stores and releases two hormones that are actually synthesized by the hypothalamus:

• Oxytocin: Acts on smooth muscles. In females, it stimulates strong uterine contractions during childbirth and milk ejection from the mammary glands.
• Vasopressin (or Antidiuretic Hormone, ADH): Acts on the kidneys to increase the reabsorption of water and electrolytes, reducing water loss through urine (diuresis).

The Pineal Gland

The pineal gland is located on the dorsal side of the forebrain. It secretes a hormone called melatonin.

Functions of Melatonin:

• Regulates the 24-hour (diurnal) rhythm of the body.
• Maintains the normal sleep-wake cycle and body temperature.
• Influences metabolism, pigmentation, the menstrual cycle, and our defense capability.

Thyroid Gland

The thyroid gland is located in the neck, with two lobes on either side of the trachea, connected by a thin tissue called the isthmus. The gland is made of follicles and stromal tissues. The follicular cells synthesize two key hormones:

• Tetraiodothyronine or Thyroxine ($T_4$)
• Triiodothyronine ($T_3$)

Iodine is essential for the production of these hormones.

Disorders of the Thyroid Gland:

• Hypothyroidism (underactive thyroid):
  • Goitre: An enlargement of the thyroid gland due to iodine deficiency.
  • Cretinism: Occurs when hypothyroidism happens during pregnancy. It causes stunted growth, mental retardation, low IQ, abnormal skin, and deaf-mutism in the baby.
  • In adult women, it can cause the menstrual cycle to become irregular.
• Hyperthyroidism (overactive thyroid):
  • Caused by cancer or nodules in the thyroid gland, leading to abnormally high levels of thyroid hormones.
  • Exophthalmic Goitre (Graves' disease): A form of hyperthyroidism characterized by an enlarged thyroid, protrusion of the eyeballs, increased metabolic rate, and weight loss.

Functions of Thyroid Hormones:

• Regulate the basal metabolic rate (BMR).
• Support the formation of red blood cells.
• Control the metabolism of carbohydrates, proteins, and fats.
• Help maintain water and electrolyte balance.

The thyroid gland also secretes a protein hormone called Thyrocalcitonin (TCT), which helps regulate blood calcium levels.

Parathyroid Gland

Humans have four parathyroid glands located on the back side of the thyroid gland (two on each lobe). They secrete a peptide hormone called Parathyroid Hormone (PTH).

Functions of PTH:

• PTH is a hypercalcemic hormone, meaning it increases blood calcium ($Ca^{2+}$) levels.
• It acts on bones to stimulate bone resorption (demineralisation), releasing calcium into the blood.
• It increases calcium reabsorption by the kidneys.
• It increases calcium absorption from digested food.

Thymus

The thymus gland is a lobular structure located on the ventral side of the aorta, between the lungs and behind the sternum. It plays a major role in the immune system.

The thymus secretes peptide hormones called thymosins.

Functions of Thymosins:

• Promote the differentiation of T-lymphocytes, which are responsible for cell-mediated immunity.
• Promote the production of antibodies, which provide humoral immunity.

The thymus gland degenerates in old individuals, leading to decreased production of thymosins and a weaker immune response.

Adrenal Gland

The body has a pair of adrenal glands, one located on top of each kidney. Each gland has two parts:

1. Adrenal Medulla (inner part)
2. Adrenal Cortex (outer part)

1. Adrenal Medulla The adrenal medulla secretes two hormones called catecholamines:

• Adrenaline (epinephrine)
• Noradrenaline (norepinephrine)

These are known as emergency hormones or hormones of Fight or Flight because they are rapidly secreted in response to stress. Effects of Catecholamines:

• Increase alertness, pupil dilation, and sweating.
• Cause piloerection (hairs standing on end).
• Increase heart rate and strength of heart contraction.
• Increase the rate of respiration.
• Stimulate the breakdown of glycogen, increasing blood glucose levels.
• Stimulate the breakdown of lipids and proteins.

2. Adrenal Cortex The adrenal cortex has three layers and secretes hormones called corticoids.

• Glucocorticoids: Involved in carbohydrate metabolism. The main one is cortisol.
• Mineralocorticoids: Regulate water and electrolyte balance. The main one is aldosterone.

Functions of Glucocorticoids (Cortisol):

• Stimulate gluconeogenesis (making glucose from non-carbohydrates), lipolysis (fat breakdown), and proteolysis (protein breakdown).
• Inhibit cellular uptake of amino acids.
• Maintain the cardiovascular system and kidney function.
• Produce anti-inflammatory reactions and suppress the immune response.
• Stimulate RBC production.

Functions of Mineralocorticoids (Aldosterone):

• Acts on the kidneys to stimulate reabsorption of sodium ($Na^+$) and water, and the excretion of potassium ($K^+$) and phosphate ions.
• Helps maintain electrolytes, body fluid volume, osmotic pressure, and blood pressure.

The adrenal cortex also secretes small amounts of androgenic steroids, which contribute to the growth of axial, pubic, and facial hair during puberty.

Pancreas

The pancreas is a composite gland that functions as both an exocrine (digestive) and endocrine gland. The endocrine part consists of about 1 to 2 million Islets of Langerhans.

The Islets have two main types of cells:

• $\alpha$-cells, which secrete glucagon.
• $\beta$-cells, which secrete insulin.

Glucagon:

• A peptide hormone that acts on liver cells (hepatocytes).
• It is a hyperglycemic hormone because it increases blood glucose levels.
• It stimulates glycogenolysis (breakdown of glycogen into glucose) and gluconeogenesis.
• It reduces cellular glucose uptake.

Insulin:

• A peptide hormone that acts on liver cells and fat cells (adipocytes).
• It is a hypoglycemic hormone because it decreases blood glucose levels.
• It enhances cellular glucose uptake and utilization.
• It stimulates the conversion of glucose to glycogen (glycogenesis).

Together, insulin and glucagon maintain blood glucose homeostasis.

Testis

A pair of testis is located in the scrotal sac of males. The testis is the primary male sex organ and also an endocrine gland. The Leydig cells (or interstitial cells) in the testis produce a group of hormones called androgens, mainly testosterone.

Functions of Androgens:

• Regulate the development and function of male accessory sex organs (e.g., prostate gland, seminal vesicles).
• Stimulate muscular growth, growth of facial and axillary hair, aggressiveness, and a low-pitched voice.
• Play a major role in spermatogenesis (sperm formation).
• Influence male sexual behavior (libido).
• Have anabolic (synthetic) effects on protein and carbohydrate metabolism.

Ovary

Females have a pair of ovaries located in the abdomen. The ovary is the primary female sex organ and also an endocrine gland. It produces two groups of steroid hormones: estrogen and progesterone.

• Estrogen is mainly synthesized by the growing ovarian follicles.
• Progesterone is mainly secreted by the corpus luteum, which forms from the ruptured follicle after ovulation.

Functions of Estrogen:

• Stimulates the growth and activities of female secondary sex organs.
• Promotes the development of growing ovarian follicles.
• Responsible for female secondary sex characters (e.g., high-pitched voice).
• Stimulates mammary gland development.
• Regulates female sexual behavior.

Functions of Progesterone:

• Supports pregnancy.
• Acts on mammary glands to stimulate the formation of alveoli (milk-storing sacs) and milk secretion.

Hormones of Heart, Kidney and Gastrointestinal Tract

Besides the major endocrine glands, other tissues also secrete hormones.

• Heart: The atrial wall of the heart secretes a peptide hormone called atrial natriuretic factor (ANF). When blood pressure increases, ANF is released, causing dilation of blood vessels, which in turn decreases blood pressure.
• Kidney: The juxtaglomerular cells of the kidney produce erythropoietin, a peptide hormone that stimulates erythropoiesis (the formation of red blood cells).
• Gastrointestinal Tract: Endocrine cells in the GI tract secrete four major peptide hormones:
  • Gastrin: Stimulates the secretion of hydrochloric acid and pepsinogen in the stomach.
  • Secretin: Stimulates the pancreas to secrete water and bicarbonate ions.
  • Cholecystokinin (CCK): Stimulates the pancreas to release enzymes and the gall bladder to release bile juice.
  • Gastric Inhibitory Peptide (GIP): Inhibits gastric secretion and motility.

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

Mechanism of Hormone Action

Hormones work by binding to specific proteins called hormone receptors, which are located only in their target tissues. This binding forms a hormone-receptor complex, which leads to biochemical changes in the target tissue.

Types of Receptors:

1. Membrane-bound receptors: Located on the cell membrane of target cells.
2. Intracellular receptors: Located inside the target cell, usually in the nucleus (nuclear receptors).

Chemical Classes of Hormones:

• Peptide, polypeptide, protein hormones: (e.g., insulin, glucagon, pituitary hormones)
• Steroids: (e.g., cortisol, testosterone, estrogen)
• Iodothyronines: (thyroid hormones)
• Amino-acid derivatives: (e.g., epinephrine)

How Different Hormones Act:

1. Hormones with Membrane-Bound Receptors (e.g., Protein hormones):

   • These hormones do not enter the target cell.
   • They bind to a receptor on the cell surface.
   • This binding triggers the generation of second messengers inside the cell (e.g., cyclic AMP, $IP_3$, $Ca^{++}$).
   • The second messengers then carry out the biochemical changes and regulate cellular metabolism.

2. Hormones with Intracellular Receptors (e.g., Steroid hormones, Thyroid hormones):

   • These hormones can pass through the cell membrane and enter the cell.
   • They bind to a receptor inside the cell (in the cytoplasm or nucleus).
   • The hormone-receptor complex then interacts with the genome (DNA) to regulate gene expression or chromosome function.
   • This ultimately results in physiological and developmental effects.