Biochemical Foundations of Human Vital Activity - Volkov, N.I., Nesen, E.N. 2000

Biochemical Foundations of Human Vital Activity
Hormones as Regulators of Metabolism
Biological Role of Hormones

Pituitary Hormones

The Pituitary Gland, situated at the Base of the Brain, is a central endocrine gland that interacts with the Hypothalamus to link the nervous and endocrine systems. Pituitary hormones coordinate the Functions of other Endocrine glands (see Fig. 49). The gland consists of three lobes: the anterior (adenohypophysis), the intermediate, and the posterior (neurohypophysis).

The anterior pituitary secretes protein hormones known as tropic hormones. These include the somatotropic hormone (STH) or Growth Hormone (GH), thyrotropic hormone (TTH), adrenocorticotropic hormone (ACTH), gonadotropic hormones (GTH), prolactin (PRL), and lipotropic hormone (LPH).

The somatotropic hormone stimulates body GROWTH AND DEVELOPMENT, increases the longitudinal growth of tubular bones, and enhances the synthesis of protein, Nucleic Acids, and Glycogen, thereby exhibiting an anabolic effect. In addition, it promotes the mobilization of fats from adipose tissue, increases their oxidation, and facilitates the Transport of Amino acids across Cell membranes. This hormone decreases The rate of carbohydrate oxidation in Tissues, which helps elevate Blood glucose levels. A deficiency of growth hormone in early childhood leads to Pituitary dwarfism without impairing intellectual development, whereas an excess results in gigantism. When growth hormone excess develops during adolescence, it can cause asymmetrical enlargement of the limbs and lower jaw, a condition known as acromegaly. Today, synthetic human-identical growth hormone is available, enabling successful Treatment of patients with secretory disorders; STH is unique in exhibiting species-specific biological activity.

The thyrotropic hormone stimulates The Thyroid Gland, increasing both the number and size of its Cells.

The adrenocorticotropic hormone maintains The Structure of the adrenal cortex and stimulates the synthesis of its hormones. In the absence of this hormone, the adrenal cortex undergoes atrophy. An elevated ACTH blood level, such as during stress, stimulates the synthesis of corticosteroids, which play a crucial role in the body's adaptation to stress.

Gonadotropic hormones, which include follicle-stimulating hormone (FSH) and luteinizing hormone (LH), regulate the function of the Gonads (Testes and Ovaries). Specifically, FSH stimulates follicular development in the ovaries and the seminiferous tubules in males; LH is involved in corpus luteum formation in females and The stimulation of Leydig cells, which produce testosterone in males. Consequently, by influencing testosterone production, gonadotropic hormones enhance anabolic processes. Reduced secretion of these hormones leads to gonadal atrophy.

The lactotropic hormone (prolactin) controls mammary gland development and milk production, as well as The production of luteinizing hormone, which influences gonadal development.

The lipotropic hormone stimulates The breakdown of fats in adipose tissue and their utilization in energy-yielding processes.

The intermediate lobe of the pituitary secretes the melanocyte-stimulating hormone, or melanotropin (MSH), which affects Skin pigmentation, dark adaptation of the eyes, and thyroid function.    

The posterior lobe of the pituitary stores two hormones: oxytocin and vasopressin (antidiuretic hormone). Oxytocin stimulates smooth Muscle contractions in the Uterus and the function of the Mammary Glands. Vasopressin raises blood pressure and regulates Water reabsorption in the Kidneys, thereby reducing daily urine output. A deficiency in this hormone leads to a drastic increase in urine output (up to 25 L⋅day^-1), causing diabetes insipidus. Consequently, this hormone plays a vital role in regulating body Water Balance and maintaining physiological blood volume.

THYROID HORMONES

The thyroid gland consists of two lobes located on the anterior surface of the Trachea, just below the Larynx (Fig. 53). It synthesizes three key thyroid hormones: thyroxine (T₄), triiodothyronine (T₃), and Calcitonin.

Thyroxine and triiodothyronine are derivatives of The amino acid Tyrosine. Their molecules contain four (T₄) or three (T₃) iodine atoms. These hormones regulate carbohydrate, lipid, and Protein METABOLISM, and stimulate Energy Metabolism by activating the mobilization and oxidation of CARBOHYDRATES and fats, thereby increasing the basal metabolic rate by 60–100%. This leads to a rise in body Temperature. Furthermore, they activate Protein Biosynthesis, stimulating overall growth and development, particularly in young organisms.

When thyroid secretory function declines (hypothyroidism) in early childhood, it causes delayed growth, delayed sexual maturation, and impaired intellectual development (cretinism). If this disorder develops in adults, the basal metabolic rate drops by 30–40% due to alterations in protein metabolism. Water accumulates in the subcutaneous tissue, resulting in edema known as Myxedema. Hypothyroidism can be caused by an iodine deficiency in diet and drinking water. In such cases, the thyroid gland enlarges, leading to endemic goiter.

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Fig. 53 Location OF THE thyroid gland

Calcitonin is a polypeptide consisting of 32 amino acid residues. It lowers blood Calcium and phosphorus levels and promotes their deposition into Bone tissue, acting oppositely to parathyroid hormone, which increases blood calcium by enhancing bone resorption and intestinal absorption, much like vitamin D (see Chapter 7).

Pancreatic Hormones

The Pancreas exhibits both exocrine and endocrine functions. Its endocrine function is carried out by the islets of Langerhans, which synthesize polypeptide hormones: Insulin, Glucagon, and Somatostatin. The islets of Langerhans contain Three types of hormone-secreting cells: alpha, beta, and delta cells (Fig. 54).

Insulin is synthesized by beta cells and regulates carbohydrate, lipid, and protein metabolism. Its effect on Carbohydrate Metabolism stems from enhancing glucose Transport from the blood into Skeletal Muscle, cardiac muscle, and adipose tissue by increasing The Cell membrane permeability of these tissues, while also stimulating glycogen synthesis in The Liver and Muscles. Thus, insulin lowers blood glucose levels, exhibiting a hypoglycemic effect. Insulin also stimulates lipid synthesis and storage in adipose tissue, the Uptake of Amino acids into cells, and their conversion into protein. Consequently, insulin promotes nutrient storage, thereby exerting an anabolic effect.

The primary stimulus for Insulin secretion is an elevation in blood glucose concentration, with Amino Acids having a similar effect. Insufficient insulin secretion leads to Diabetes Mellitus, characterized by high blood glucose levels (hyperglycemia) and the presence of glucose in the urine (glucosuria). Tissues begin to utilize fats as their primary energy source, which ultimately results in diabetic coma and death. Administering insulin to patients with diabetes mellitus partially normalizes metabolic processes and saves their lives.

Glucagon is synthesized by the alpha Cells of the pancreatic islet tissue. Its effects are antagonistic to those of insulin. Glucagon stimulates Glycogenolysis in the liver, thereby raising blood glucose levels; it also promotes hepatic glucose production from Amino Acids and fats when glycogen stores are depleted, and activates lipolysis in adipose tissue. Therefore, its action is directed toward mobilizing the body's energy reserves during increased energy demands.

The factor regulating glucagon release from the pancreas, much like insulin, is the Blood Glucose Level. In contrast to insulin, glucagon secretion increases when glucose levels drop and decreases when they normalize. Both hormones act together to maintain blood glucose Homeostasis (Fig. 55).

Somatostatin is secreted by pancreatic delta cells as well as the pituitary gland (see Fig. 48). It inhibits the release of both insulin and glucagon from their respective secretory cells.

Fig. 54 Hormone-secreting cells (islets of Langerhans) of the pancreas

Fig. 55 Joint Regulation of Blood glucose levels by insulin and glucagon

Adrenal hormones

The Adrenal Glands are located at the upper poles of the kidneys. Each Adrenal gland consists of two layers: an outer cortex and an inner medulla (Fig. 56). They synthesize various hormones with specific biological functions. The adrenal cortex produces about 40 Steroid Hormones known as corticosteroids, which are divided into three main groups: glucocorticoids, mineralocorticoids, and gonadocorticoids.

Glucocorticoids include cortisol (hydrocortisone) and corticosterone. These hormones enhance the hepatic Synthesis of glucose from non-carbohydrate precursors (amino acids, Fatty acids) and prevent sharp drops in blood glucose levels during fasting or physical exertion, for instance. In muscles, skin, and adipose tissue, they stimulate the Breakdown of Proteins and fats to be used as Energy Sources. This action of glucocorticoids plays a vital role in the body's adaptation to various stressors—such as cold, starvation, fear, and intense physical exertion—by mobilizing nutrient reserves from peripheral tissues and preventing the depletion of hepatic glycogen stores. The liver also synthesizes new proteins, including adaptogenic Enzymes required to stimulate adaptive processes.

Mineralocorticoids are represented primarily by aldosterone, which regulates Mineral Metabolism (sodium and potassium) and water balance.

Fig. 56 Localization of the adrenal glands and their two layers: the cortex and the medulla

Aldosterone promotes the retention of sodium and water in the body while excreting potassium, thereby controlling Blood Plasma volume as well as the cellular balance of sodium and potassium. Its secretion increases when plasma volume decreases. A deficiency in mineralocorticoids leads to dehydration, which negatively impacts overall physiological function.

Gonadocorticoids are primarily Male Sex Hormones (androgens), with minor amounts of Female Sex Hormones (estrogens). They regulate the same functions as the Hormones of the gonads, though to a lesser extent.

The adrenal medulla synthesizes two hormones: adrenaline (epinephrine) and noradrenaline (norepinephrine), collectively known as catechols (catecholamines). As noted above, both hormones are synthesized from the amino acid tyrosine under The Influence of nerve impulses. Noradrenaline is also produced in the nerve endings of the sympathetic Nervous system, serving as its neurotransmitter. Both hormones play a crucial role in the body's adaptive responses, particularly under stress.

Adrenaline and noradrenaline stimulate the mobilization of the body's energy reserves, enhance glycogenolysis in the liver, and raise blood glucose levels. These hormones also promote glycogen breakdown in skeletal muscles, glucose oxidation via Glycolysis, and the breakdown of stored fats in adipose tissue. Along with mobilizing energy resources, they cause constriction of small Arteries while dilating the coronary Vessels of the Heart and the Blood Vessels of skeletal muscles, thereby improving Blood supply and function in these tissues.

American physiologist W. Cannon termed adrenaline the "hormone of fear, fight, or flight." Exposure to a stressor increases the release of catecholamines into the blood, which, In addition to the effects mentioned above, stimulates the production of pituitary hormones (ACTH) and hormones of the adrenal cortex. The latter ensure The Development of adaptive changes that increase the body's resistance to stress factors (see Chapter 13).

Hormones of the Reproductive Glands

Sex hormones are synthesized primarily in the gonads: the testes in males and the ovaries in females. Small quantities are also produced in the adrenal cortex and the Placenta.

The male gonads synthesize steroid hormones known as androgens, the principal representative being testosterone. Testosterone production begins in the Leydig cells during Puberty (at ages 12–14) under the Influence of the pituitary luteinizing hormone. Testosterone exhibits both androgenic and anabolic effects. Its androgenic action is associated with the development of secondary sex characteristics (voice pitch, male body habitus, etc.) and The regulation of reproductive function. Androgens also accelerate the closure of bone growth plates. The anabolic action of testosterone relates to its influence on protein metabolism. This hormone and other androgens enhance Protein Synthesis in the liver, kidneys, and particularly in skeletal muscles. Consequently, androgens and their synthetic analogues are used in clinical medicine and sports to accelerate recovery from illness or intense physical activity, as well as to build muscle mass. The induction of protein synthesis, including enzymes, leads to enhanced energy production. Nevertheless, The Use of hormonal anabolic agents in sports to boost athletic performance is prohibited by the International Olympic Committee. Steroid anabolics are classified as doping agents because they have adverse effects on athletes' health.

The female gonads synthesize steroid hormones known as estrogens. The principal estrogens are estradiol and progesterone. Estrogens regulate the Menstrual cycle and reproductive function, as well as the development of secondary sex characteristics. They stimulate protein synthesis in the uterus—especially during Pregnancy—as well as in The Heart and liver, exerting an anabolic effect, while also enhancing catabolic reactions in skeletal muscles.

Progesterone is synthesized by the cells of the corpus luteum and regulates uterine function during the second half of the menstrual cycle. It stimulates processes essential for the establishment and maintenance of pregnancy while inhibiting estrogen production. Under the influence of progesterone (acting alongside estrogens), the uterus enlarges, enabling the fertilized egg to implant in its wall and the fetus to develop. Progesterone also promotes mammary gland development. Its absence during pregnancy leads to fetal demise.