BIOLOGICAL ACTION OF HORMONES

 1. Glucocorticoids: structure of cortisol, target tissues, effects on metabolism and functions. 

Hyper- and hypoproduction of the hormones. 

2. Mineralocorticoids: structure of aldosterone, target tissues, biological effects. Hyper- and 

hypoproduction of the hormones. 

3. Female sex hormones: structure of estradiol and progesterone, target tissues, effects on 

metabolism and functions. Hyper- and hypoproduction of the hormones. 

4. Male sex hormones: structure of testosterone, target tissues, effects on metabolism and 

functions. Hyper- and hypoproduction of the hormones. 

5. Hormones of hypothalamus and hypophysis, their biological action. Growth hormone, 

adrenocorticotropic hormone: target tissues, effects on metabolism. Hyper- and 

hypoproduction of growth hormone. 

6. Eicosanoids (prostaglandins, thromboxanes, leukotrienes) and their role in the regulation 

of metabolism and functions. 

7. Disorders of functions of endocrine glands: hyper- and hypoproduction of hormones.

ADRENAL CORTEX produces steroid hormones: 

1. Glucocorticoids 

2. Mineralocorticoids 

3. Male and female sex hormones.   

1. Glucocorticoids: structure of cortisol, target tissues, effects on metabolism and functions. Hyper- and hypoproduction of the hormones. 

01. Glucocorticoids (GCs): cortisol, cortisone and corticosterone.

Structure of cortisol 

Target-tissues for GCs:

1.      Liver

2.      Muscle

3.      Adipose

4.      Connective

5.      lymphoid tissues

•       In the liver, GCs ↑ anabolic processes and ↑ transport of substrates into the cell (↑ permeability of membranes), and

In the other target-tissues GCs ↑ catabolism and ↓ transport of substrates into the cell (↓ permeabilityj of membranes). 

metabolism GCs can influence: 

•       Асtion of glucocorticoids

1.      on METABOLISM 

2.      SYSTEMIC action

1)  Carbohydrate metabolism 

2)  Lipid metabolism 

3)  Protein and amino acid metabolism

 

The effects of GCs on metabolism 

01. Carbohydrate metabolism. 

GCs ↓ glycolysis in all the target-tissues.  

•       In the liver, GCs ↑ gluconeogenesis and synthesis of glycogen.

•       In the other tissues, GCs ↓ transport of glucose into the cell (↓ permeability of membranes).

The excess of GCs ↑ the blood glucose level and may cause steroid diabetes.

02. Lipid metabolism.

•       In the liver, GCs ↑ synthesis of fats (triacylglycerols), VLDL, and ketone bodies.

•       In the adipose tissue GCs ↑ degradation of triacylglycerols on the extremities but ↑ deposition of the triacylglycerols on the trunk and on the face.

The excess of GCs causes the spider-like obesity, and ↑ [ketone bodies] in the blood.       

03. Protein and amino acid metabolism. 

•       In the liver, GCs ↑ synthesis of protein and ↓ its degradation.

•       In the other target-tissues, GCs ↓ synthesis of protein, ↑ its degradation.

The excess of GCs leads to: 

-         muscle atrophy and weakness; 

-         the decrease of collagen synthesis → bone fragility and fractures at minimal trauma; slowdown of wounds’ healing; 

-         in the lymphoid tissue GCs decrease synthesis of antibodies, lymphocyte formation and cause destruction of these cells 

•       ↑ susceptibility to infections.

•       used for treatment of some allergic reactions

•       GCs are used in transplantation of organs because they suppress the immune response

Systemic effects of GCs:

1)  ↑ secretion of HCl in the stomach (GCs ↓ synthesis of prostaglandins which ↓ secretion of HCl). The excess of GCs may cause stomach ulcers.

2)  GCs have anti-inflammatory effect and may be used for treatment of inflammation. (GCs ↓ synthesis of prostaglandins – tissue inflammatory factors).

3)  ↓ hypersensitivity of the organism, and may be used for treatment of allergy (e.g. anaphylactic shock).

 

 

2. Mineralocorticoids: structure of aldosterone, target tissues, biological effects. Hyper- and hypoproduction of the hormones.

Aldosterone and dehydroxycorticosterone regulate metabolism of Na+, K+ and water in the organism. 

Structure of aldosterone

 

The target-tissue: 

epithelial cells of the distal renal tubules.

Aldosterone is called sodium-retaining hormone because in the kidney it ↑ reabsorption of Na+ from the urine and ↑ [Na+].

Water follows the flow of Na+ → → the ↑ of the circulating blood volume. 

The excess of aldosterone → → the ↑ BP and edema (swelling of tissues).

The sodium reabsorption increases the potassium excretion in urine.

Aldosterone ↑ excretion of K+ into the urine. 

The excess of aldosterone leads to the ↓ of [K+] in the blood → → heartbeat impairments, heart failure, and heavy weakness.

Sweat glands are another target-tissue for aldosterone. 

The heat (high outer temperature) stimulates aldosterone production due to which the excessive sodium loss via the sweat is prevented. 

Deficiency of aldosterone in the organism results in the loss of sodium and water with the urine and dehydration of the body. 

Glucocorticoids, especially corticosterone, exert partial mineralocorticoid effects on the organism; therefore in the use of glucocorticoids as therapeutic agents, the potassiumcontaining medicines should be prescribed to the patient.

 

Hypercorticoidism 3 types: 

1.     Glucocorticoid excess (hyperfunction of zona fasciculata of adrenal cortex) Cushing’s syndrome (malignant adrenal cortex tumor) Cushing’s disease (benign enlargement of the adrenal glands).

2.     Mineralocorticoid excess (hyperfunction of zona arcuata) - Konn’s disease.

3.     Adrenal virilism, or adrenogenital syndrome (hyperproduction of male sex hormones in zona reticulata of adrenal cortex).

In females, this leads to virilism (appearance of male signs);

in males, the ↑ of male signs; in children – premature sex developing (maturation before puberty).

 

Hypocorticoidism (Addison’s disease or bronze disease) 

This is hypofunction of the adrenal cortex, ↓ both mineralocorticoids and glucocorticoids.

Symptoms: bronze pigmentation of the skin, weakness, hypoglycemia (hunger intolerance), subconscious preference of salt meals, the ↓ BP.

 

3. Female sex hormones: structure of estradiol and progesterone, target tissues, effects on metabolism and functions. Hyper- and hypoproduction of the hormones.

01.  ESTROGENS 

- estradiol (is formed in ovaries),

- estriol (in placenta),

- (in adrenal cortex),

02. PROGESTERON (is formed by corpus luteum of ovaries).

- responsible for the preparation and maintenance of the uterus

The target-tissues and effects:

•  sex organs – development and functioning of sex organs;

•  non-sex organs:

1)  CNS: formation of sexual behaviour, instinct, and psychical status of a female.

2)  Bones, larynx: formation of the female type of the skeleton, larynx and voice.

Estrogens ↑ ossification of epiphyses where the growth zone of the bone is located.

In a girl, lack of estrogens may cause tall height.

In women, excess of estrogens ↑ deposition of Ca in the bone cavities where the red bone marrow is located; therefore anemia may take place.

3)  Skin – ↑ growth of hair on the female type, ↓ hair growth on the trunk and face, ↓ secretory activity of the sebaceous glands.

4)  Adipose tissue – ↑ synthesis of triacylglycerols, promote formation of the typically female fat depositions.

 

5)  Kidney – 

- estrogens ↑ retaining of Na+ in the organism, 

 - progesterone ↑ excretion of Na+ into the urine. 

In pregnancy (much progesterone) the loss of Na+ with the urine explains the subconscious preference of the salt food.

6) Liver. Estrogens ↑ synthesis of: 

a)   blood clotting factors (II, VII, IX, X) and angiotensinogen; excess of estrogens may cause thromboses and hypertension (↑BP).

b)   VLDL and HDL; VLDL transfer triacylglycerols from the liver to adipose tissue, therefore, in female, muscles are always covered by the layer of subcutaneous adipose tissue.

HDL remove cholesterol off the organism; therefore atherosclerosis and myocardial infarction (as consequences of the increased cholesterol level in the blood) are more often observed in men than in women.

 

4. Male sex hormones: structure of testosterone, target tissues, effects on metabolism and functions. Hyper- and hypoproduction of the hormones.

MALE SEX HORMONES (androgens): testosterone and androsterone. They are formed in 

1.     testes, 

2.     adrenal cortex, 

3.     prostate gland.

They are also formed in ovaries

Androgens are inactivated in the liver with the resultant formation of 17-ketosteroids which are excreted into the urine. 

Androgens exert generalized anabolic effect on the organism:they stimulate synthesis of nucleic acids and proteins, retain nitrogen and calcium in the organism, and increase synthesis of the membrane phospholipids.

Structure of testosterone 

The target-tissues and effects:

•  sex organs – the hormones exert androgenic effect (development and functioning of sex organs).

•  non-sex organs:

1)  CNS: formation of sexual behaviour, instinct, and psychical status of a male. Excess of androgens may cause aggressiveness.

2)  Bones, larynx: formation of the male type of the skeleton, larynx and voice.

Androgens ↑ ossification of epiphyses (the growth zone of the bone).

The excess of androgens may lead to the short height.

3)  Muscles – ↑ synthesis of protein in the skeletal muscle, its mass and strength.

4)  Adipose tissue – ↓ synthesis of triacylglycerols and ↑ their degradation; therefore in men the subcutaneous fat layer is thinner than in women.

5)  Skin – ↑ growth of hair on the male type, stimulate hair growth on the trunk and face, pigmentation of the skin, secretory activity of the sebaceous glands. 

Excess of androgens may be a reason of baldness ( the absence of hair on the head).

 

5. Hormones of hypothalamus and hypophysis, their biological action. Growth hormone, adrenocorticotropic hormone: target tissues, effects on metabolism. Hyper- and hypoproduction of growth hormone.

THE SYSTEM OF HYPOTHALAMUS-HYPOPHYSIS IN REGULATION OF ENDOCRINE GLANDS

Synthesis of hormones and their secretion into the blood are regulated by the requirements of the organism. 

Hormones are released into the blood in response to the appropriate stimulation. 

The impulses from receptors reach (via afferent nerves) the CNS, there the impulses are analyzed and then (via efferent nerves) sent to the periphery. 

But the nervous regulation doesn’t cover all functions of all organs; therefore it is supplemented by hormonal regulation. 

The site of joining the nervous and hormonal regulation is the hypothalamus. 

Under the influence of nervous impulses from the CNS, liberins and statins are formed in hypothalamus.

Liberins stimulate and statins inhibit synthesis of tropic hormones of the hypophysis (pituitary gland), i.e. the anterior lobe of hypophysis known as adenohypophysis. 

Hormones generated here enter the blood, are transported to the peripheral endocrine glands and stimulate production of definite hormones. 

The hormones of adenohypophysis include: 

1.     Growth hormone (GH; somatotropin) acts on the bone tissue to accelerate its growth.

2.     Thyroid stimulating hormone (TSH) stimulates growth of the thyroid gland and secretion of thyroxine. 

3.     Adrenocorticotropic hormone (ACTH) stimulates growth of the adrenal cortex and increases mainly secretion of cortisol. 

4.     Gonadotropic hormones: follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (or lactotropic hormone, LTH). 

They influence development and the hormone secretion of ovaries in females and testes in males. 

Prolactin stimulates lactation. 

The posterior lobe of hypophysis called neurohypophysis contains hormones oxytocin and vasopressin which are synthesized in supraoptical and paraventricular nuclei of hypothalamus but are stored in the posterior lobe of the hypophysis. 

1.                Oxytocin stimulates the uterus to contract during the childbirth and causes production of milk from the mammary glands. 

2.                Vasopressin, or antidiuretic hormone (ADH) stimulates reabsorption of water by the kidney tubules and causes vasoconstriction resulting the increase of the blood pressure. In the posterior lobe atrophy, diabetes insipidus is developed (urinary excretion is extremely large, 10-20 liters per day). 

Of all hormones produced in the adenohypophysis, growth hormone and ACTH exert the most expanded biochemical and physiological effects on the organism.

 

 GROWTH HORMONE, its action

1)  Anabolic effect. GH ↑ synthesis of nucleic acids and proteins in bones, cartilages, and soft tissues.

2)  Diabetogenic effect. In the liver, GH ↑ gluconeogenesis. 

In the muscle and adipose tissue, GH ↓ membrane permeability for glucose to enter the cell. 

Excess of GH leads to the insulinoresistancy of peripheral tissues and results in somatotropic diabetes.

3)  Lipolytic effect. In children, the adipose stores are absent because in the adipose tissue GH ↑ cleavage of triacylglycerols. 

Due to lipolytic effect and further utilization of fatty acids, in excess of GH, the ↑ amount of ketone bodies is produced in the liver and their concentration in the blood ↑.

Hypersecretion of GH

In childhood, this leads to gigantism: excessive height, the extremities are disproportionally long.

In adults, this results in acromegaly: intensive enlargement of individual parts of the skeleton bones (superciliary archs, cheekbones, jaw and chin), enlargement of the soft tissues of the face (lips, nose, tongue). 

Hands and feet are also abnormally large. Hyposecretion of GH (dwarfism)

in childhood leads to the proportional underdevelopment of the skeleton and the whole body. 

Unlike in cretinism, no psychic abnormalities and no skeletal deformations.

ACTH: 

target tissues and effects 

1)adrenal cortex – ↑ synthesis and secretion of glucocorticoids and (to less extent) mineralocorticoids;

2)adipose tissue – ↑ cleavage of triacylglycerols; 3) liver – ↑cleavage of glycogen.

 

6. Eicosanoids (prostaglandins, thromboxanes, leukotrienes) and their role in the regulation of metabolism and functions. 

PROSTAGLANDINS AND OTHER EICOSANOIDS

This is a group of local, or tissue hormones, or hormone-like substances, because unlike “real” hormones that are synthesized in one type of organs but act in the other one, eicosanoids are both formed and act at the same tissues. 

These substances are called eicosanoids because they are produced from eicosatetraenoic, or arachidonic, acid.

Eicosanoids (prostaglandins, prostacyclins, thromboxanes, and leukotrienes) are synthesized from arachidonic acid (Fig. 14.1.). 

-         This polyunsaturated fatty acid is released from membrane phospholipids by phospholipase A2. 

-         The enzyme is inhibited by glucocorticoids (antiinflammatory agents). 

-         Arachidonic acid is oxidized by cyclooxygenase to form prostaglandins, prostacyclins and thromboxanes. 

-         Cyclooxygenase is inhibited by aspirin, indomethacin, and other nonsteroidal antiinflammatory agents. 

-         Leukotrienes can be produced from arachidonic acid by a pathway in which lipoxygenase participates; its activity is inhibited by vitamin E, and vitamin P.

Prostacyclins dilate arteries, ↓ aggregation of platelets. 

Thromboxanes cause vasoconstriction and ↑ aggregation of platelet.

Leukotrienes take part in inflammation, allergic reactions, and immune response, attract leucocytes to the place of inflammation, constrict bronchi, and ↑ secretion of bronchial mucus.

Prostaglandins are synthesized in all cells excepting erythrocytes, and degraded very quickly – in 20 minutes.

Major classes of prostaglandins which have clinical importance:

-         Prostaglandins E 

-         Prostaglandins F Prostaglandins E:

1)  ↓ cleavage of triacylglycerols and glycogen; 

2)  are the tissue inflammatory factors; ↑ permeability of vessels and cell membranes, dilate capillaries; they are pyrogenic agents, i.e. they ↑ the body t° ; therefore aspirin (as an inhibitor of prostaglandin synthesis) is used to ↓ t°.

3)  cause pulsating headache, which may be revealed in 20 minutes by the administration of aspirin;

4)  ↓ BP, therefore they are used in treatment of hypertension;

5)  dilate bronchi, therefore may be used in treatment of bronchial asthma;

6)  ↓ secretion of HCl in the stomach, therefore are used in the therapy of ulcers (aspirin and glucocorticoids ↓ synthesis of prostaglandins which ↓ HCl secretion; therefore the improper use of aspirin or the prolonged therapy with glucocorticoids may lead to ulcers in the stomach);

Prostaglandins F:  

-         stimulate peristalsis of the bowel; 

-         constrict bronchi; 

-         stimulate the smooth muscle of the uterus, therefore they are used for infant delivery.

 

7. Disorders of functions of endocrine glands: hyper- and hypoproduction of hormones.