Principles of Hormonal Regulation

Principles of hormonal regulation

Hormones are substances which can change the status, function, metabolism and structure of body organs and tissues.

True hormones are released into blood stream Act only on target cells Active in very low doses May stay active for months

Types of hormone action

Metabolic

Morphogenic

Kinetic

Corrective

Hormones classification Biochemical classification:1. Steroids2. Amino-acid derivatives3. Protein-peptide compounds

Functional classification:1. Effectory2. Tropic3. Neuroregulatory (liberins & statins)

1. The hormones combine with their receptors on the outer surface of target cell membranes.

2. Activation of adenylate cyclase on the cytoplasmic side of the membranes.

3. Conversion of ATP to cyclic AMP (cAMP) within the cytoplasm.

4. cAMP activates protein kinase.5. Protein kinase phosphorylates enzymes.6. The activity of specific enzymes is either increased or

inhibited by phosphorylation.7. Changes in cell metabolism, permeability or functions.

SEQUENCE OF EVENTS INVOLVING CYCLIC AMP AS A SECOND MESSENGER

Mechanism of action of lipid solvable Mechanism of action of lipid solvable hormoneshormones

Regulation of hormone secretion by the level of effectory hormones in blood

Regulation of thyroid hormones secretion

Regulation of sex hormones secretion

Inhibitssensitivity to

releasinghormones

Thyroid gland hormones’ effects

Increase metabolism by activating enzymes & increasing oxygen consumption

As the result increase heat production and body temperature

Morphogenic influence (especially CNS & bone tissue)

Activate protein synthesis by increasing membrane permeability for amino acids

Activate lipids breakdown

Thyroid gland hormones’ effects

Increase glucose level in blood plasma by intensifying glucose absorbtion in the intestines

Activate gluconeogenesis and glucogenolysis Inactivate insuline by activation of liver insulinase Increase heart rate and cardiac output by increasing

adrenoreceptors sensitivity to adrenalin and increasing the number of receptors

Activate erythropoesis

Regulation of hormone secretion by the regulated parameter

Disease States Both increased and decreased secretion of parathyroid hormone are

recognized as causes of serious disease in man and animals. Excessive secretion of parathyroid hormone is seen in two forms: Primary hyperparathyroidism is the result of parathyroid gland disease,

most commonly due to a parathyroid tumor (adenoma) which secretes the hormone without proper regulation. Common manifestations of this disorder are chronic elevations of blood calcium concentration (hypercalcemia), kidney stones and decalcification of bone.

Secondary hyperparathyroidism is the situation where disease outside of the parathyroid gland leads to excessive secretion of parathyroid hormone. A common cause of this disorder is kidney disease - if the kidneys are unable to reabsorb calcium, blood calcium levels will fall, stimulating continual secretion of parathyroid hormone to maintain normal calcium levels in blood. Secondary hyperparathyroidism can also result from inadequate nutrition - for example, diets that are deficient in calcium or vitamin D, or which contain excessive phosphorus (e.g. all meat diets for carnivores). A prominent effect of secondary hyperparathyroidism is decalcification of bone, leading to pathologic fractures or "rubber bones".

There is no doubt that chronic secretion or continuous infusion of parathyroid hormone leads to decalcification of bone and loss of bone mass. However, in certain situations, treatment with parathyroid hormone can actually stimulate an increase in bone mass and bone strength. This seemingly paradoxical effect occurs when the hormone is administered in pulses (e.g. by once daily injection), and such treatment appears to be an effective therapy for diseases such as osteoporosis.

Inadequate production of parathyroid hormone - hypoparathyroidism - typically results in decreased concentrations of calcium and increased concentrations of phosphorus in blood. Common causes of this disorder include surgical removal of the parathyroid glands and disease processes that lead to destruction of parathyroid glands. The resulting hypocalcemia often leads to tetany and convulsions, and can be acutely life-threatening. Treatment focuses on restoring normal blood calcium concentrations by calcium infusions, oral calcium supplements and vitamin D therapy.

The effect of somatotropic hormone on protein metabolism: 1. stimulates the passing of amino acids into the cells; 2. activates the synthesis of proteins, DNA, RNA. carbohydrate metabolism: 1. activates the insulinase of liver;2. inhibits the conversion of lipids to carbohydrates;3. activates the exit of glucose from liver;4. inhibits the entry of glucose into the cells. lipid metabolism: 1. stimulates lipolysis;2. stimulates the oxidation of fatty acids.The deficiency of somatotropic hormone in children

age causes nanism. Nanism - proportional underdevelopment of all body.

Gigantism at hyperproduction of STH in children, nanism at hypoproduction in children

Acromegaly at hyperproduction of STH in grown-ups

Hormones of pancreas

Insulin. Chemical structure: protein

Effect of insulin on carbohydrate metabolism: increases the permeability of cell membranes of skeletal

muscles, adipose tissue and liver for glucose; activates the first enzyme of glycolysis - glucokinase and prevent

the inactivation of hexokinase; activates some enzymes of Krebs cycle (citrate synthase); activates the pentose phosphate cycle; activates glycogen synthetase; activates pyruvate dehydrogenase and -ketoglutarate

dehydrogenase; inhibits the gluconeogenesis; inhibits the decomposition of glycogen.

Effect of insulin on protein metabolism: increases the permeability of cell membranes for amino acids; activates synthesis of proteins and nucleic acids; inhibits the gluconeogenesis.Effect of insulin on lipid metabolism: enhances the synthesis of lipids; promotes the lipid storage activating the carbohydrate

decomposition; inhibits the gluconeogenesis.Effect of insulin on mineral metabolism: activates Na+, K+-ATP-ase (transition of K into the cells and Na

from the cells).

The deficiency of insulin causes diabetes mellitus.

Glucagon.

Chemical structure: polipeptide Functions: enhances the glycogen splitting in liver; activates the lipolisis; stimulates the gluconeogenesis.

Somatostatine. Somatostatine is produced by hypothalamus, intestine and -cells

of pancreas). Functions: inhibits the secretion of insulin and glucagon; inhibits secretion of somatotropic and thyrotropic hormones; inhibits secretion of tissue hormones of alimentary tract.Lipocain. Lipocain is produced in the epithelium cells of pancreatic ducts. Functions: activates the formation of phospholipids in liver and stimulates

the action of lipotropic alimentary factors; activates the oxidation of fatty acids in liver.

Typical findings in Cushing’s syndrome Caused by prolonged decrease in plasma

corticoids Increased protein catabolism results in : Thin skin Poor muscle development Poor wound healing Bruisability with ecchymoses Thin and scraggy hair

Typical findings in Cushing’s syndrome Redistribution of body fat : thin extremities, fat

collects in the abdominal wall, face, upper back

Purple striae (subdermal tissue rapture due to increased subcutaneous fat depots)

osteoporosis