1. GENERAL PRINCIPLES OF METABOLISM REGULATION.
HORMONES.

2. Levels of the homeostasis regulation
Highest level –
nervous system
Intermediate -
hormonal
regulation
Intracellular
(enzymes)

3. Hormones – organic biologically active compounds of different chemical nature that are produced by the endocrine glands, enter directly into blood and accomplish humoral regulation of the metabolism of compounds and functions on the organism level.
Hormonoids (tissue hormones) – compounds that are produced not in glands but in different tissues and regulate metabolic processes on the local level, but some of them (serotonin, acetylcholine) enter blood and regulate processes on the organism level.

4. Specific stimulus for hormones secretion is:
nervous impulse
concentration of the certain compound in blood passing through the endocrine gland

5. Endocrine glands: 1. Hypothalamus 2. Pituitary 3. Epiphysis 4. Thymus
5. Thyroid gland
6. Parathyroid glands
7. Langergans’ islands of pancreas
8. Epinephrine glands
9. Sex glands

7. Classification of hormones according to chemical nature
Proteins: hormones of anterior pituitary (except ACTH), insulin, parathyroid hormone.
Peptides: ACTH, calcitonin, glucagon, vasopressin, oxytocin, hormones of hypothalamus (releasing factors and statins).
Derivatives of amino acids: catecholamins (epinephrine and norepinephrine), thyroxin, triiodthyronin, hormones of epiphysis.
Steroid (derivatives of cholesterol): hormones of the cortex of epinephrine lands, sex hormones.
Derivatives of polyunsaturated fatty (arachidonic) acids: prostaglandins.

8. Fate of hormones in the organism
Are secreted directly into the blood
Peptide and protein hormones are secreted by exocytosis
Steroid (lipophilic) hormones continuously penetrate the membrane (they are not accumulated in cells, their concentration in blood is determined by the speed of synthesis)

9. Transport of hormones in blood
Protein and peptide nature – in free state
Steroid hormones and hormones of thyroid gland – bound with alpha-globulins or albumins
Catecholamines – in free state or bound with albumins, sulphates or glucuronic acid
Reach the target organs
Cells have the specific receptors to certain hormone

10. Receptors of hormones Two groups:
placed on the surface of membrane – peptide and protein hormones, prostaglandins;
placed inside the cells (cytoplasm, nucleus) – steroid and thyroid hormones

11. Model of the insulin receptor ( Jacobs, Cautrecasas, 1982)
                                                                                                  
Model of the insulin receptor ( Jacobs, Cautrecasas, 1982)

12. Inactivation of hormones
After biochemical effect hormones are released and metabolized
Hormones are inactivated mainly in liver
Inactive metabolites are excreted mainly with urine
Half-time life
from several min to 20 min – for the majority of hormones
till 1 h – for steroid hormones
till 1 week – for thyroid hormones

13. THE FINAL EFFECTS OF HORMONES ACTION
Change the permeability of cell membrane, accelerate the penetration of substrates, enzymes, coenzymes into the cell and out of cell.
Acting on the allosteric centers affect the activity of enzymes (Hormones penetrating membranes).
Affect the activity of enzymes through the messengers (cAMP). (Hormones that can not penetrate the membrane).
Act on the genetic apparatus of the cell (nucleus, DNA) and promote the synthesis of enzymes (Steroid and thyroid hormones).

14. HYPOTHALAMUS
It is located in the base of forebrain between thalamus and pituitary gland.
Has wide anatomical bonds and collects information from another structures of brain.
Collect information from blood flowing through hypothalamus.

15. Tight anatomical bonds with pituitary gland
Two groups of hormones related to anterior and posterior lobes of pituitary

16. Hypothalamus and posterior lobe of pituitary
3 peptides are synthesized
Migrate along axons into posterior lobe of pituitary
Antidiuretic hormone (vasopressin)
Oxytocin
Neurophysin (promotes transport of vasopressina and oxytocin into pituitary gland)

17. Hypothalamus and anterior pituitary
Bound with anterior pituitary by the capillary net – hypothalamic portal system
Releasing factors and statins rich the anterior pituitary via this system

18. Secretion of liberins and statins by hypothalamus is carried out under the effect of nervous impulses and as result of the change of concentrations of certain hormones in blood (feedback regulation).
Releasing factors (liberins) stimulate secretion of pituitary hormones; statins - inhibit.
somatoliberin,
thyroliberin,
corticoliberin,
foliliberin,
prolactoliberin,
luteinising-hormone liberin,
melanoliberin
somatostatin,
prolactostatin,
melanostatin

19. HYPOPHISIS - “conductor of the hormonal orchestra of the organism”
There are hormones of anterior, posterior and intermediate lobes of pituitary gland.
The most important – anterior lobe (secrets tropic hormones)
Tropic – because stimulate functions of peripheral endocrine glands

20. TROPIC HORMONES OF PITUITARY Somatotropic hormone (growth hormone)
Chemical nature – simple protein
It is secreted continuously during the whole life
Secretion is stimulated by somatoliberin, is inhibited by somatostatin
Main function – stimulates somatic growth of organs and tissues, particularly bones, cartilages, muscles.

21. Acts both directly and through the stimulation of the formation of polypeptides somatomedins (insulin-like growth factors).
ILGF are synthesized in liver

22. The effect of STH on the protein metabolism
Promotes the entrance of AA into cells,
Inhibits catabolism of proteins and AA
Activates the synthesis of proteins, DNA, RNA.
The effect of STH on the carbohydrate metabolism
Antiinsulin hormone – activates insulinase of liver
Activates the exit of glucose from liver
Inhibits the conversion of glucose into fat
The effect of STH on lipid metabolism
Stimulates the decomposition of lipids (lipolisis)
Stimulates the oxidation of fatty acids.

23. In the inherited hypoplasia of pituatary gland dwarfism is developed.
For the treatment GH is used.

24. Yao Defen, the tallest women in the life, 2.36 м
Hyperproduction of GH before puberty and before the completion of ossification results in gigantism
Yao Defen, the tallest women in the life, м

25. Hyperfunction of pituitary inadults results in acromegaly – unproportionally intensive growth of particular body parts (fingers, nose, lower jaw, tongue, inner organs).
Cause – tumor of anterior pituitary

26. Adrenocorticotropic hormone (АCTH)
Chemical nature – polipeptide
Secretion is stimulated by corticoliberin
Feedback regulation of the speed of secretion depending on the cortisol level
Controls the cortex of epinephrine gland where cortisol is produced:
promotes the increase of cholesterol content in epinephrine glands cortex and its conversion into corticosteroids;
activates the passing of glucose into epinephrine glands and pentose phosphate cycle (NADPH synthesis)
has melanocyte stimulating activity

27. Cushing’s disease
Cushing's disease – hyperproduction of ACTH (adenoma in a pituitary gland) which in turn elevates cortisol.
Obesity, particularly of the trunk and face (“moon face“) with sparing of the limbs; striae (stretches of the skin)
Proximal muscle weakness
Hirsutism (facial male-pattern hair growth)
Insomnia, impotence, amenorrhoea, infertility
Heart diseases, hypertension
Polyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes)
Kidney bones
Depression, anxiety
Hyperpigmentation

28. Thyrotropic hormone (ТТH)
Chemical structure – protein (glycoprotein)
Secretion is stimulated by thyroliberin
The speed of secretion is regulated according to the feedback regulation by thyroid hormones
It is necessary for the normal functioning of thyroid gland:
promotes the accumulation of iodine in thyroid gland and its insertion into tyrosine;
stimulates the synthesis of try- and tetraiodthyronin

29. Gonadotropic hormones Follicle-stimulating гормон
Chemical nature – protein (glycoprotein)
Secretion is stimulated by foliliberin
Function: stimulates the function of follicles in women and spermatogenesis in men
Luteinizing hormone
Chemical nature – protein (glycoprotein)
Secretion is stimulated by luliberin
Function: stimulates the follicular growth and conversion of the follicle into a corpus luteum n women and secretion of testosterone in men

30. Prolactin Chemical nature – protein
Secretion is stimulated by prolactoliberin
Functions:
-stimulates the function of mammary glands (lactation);
-provides the body with sexual gratification after sexual acts
-stimulates the function of corpus luteum (progesterone secretion);
-stimulates the growth of tissue of prostatic gland in men;
-responsible for the mother instinct

31. Lipotropic hormones Chemical nature – simple proteins Functions:
-mobilization of lipids from depot;
-melanocyte stimulating function;
-decrease Ca in blood

32. THE INTERMEDIATE LOBE OF PITUITARY
Melanocyte stimulating hormone (melanotropin)
Chemical nature – peptide
Functions:
-stimulates melaninogenesis;
-adaptation of vision in darkness

33. POSTERIOR LOBE OF PITUITARY Vasopressin (antidiuretic hormone)
Chemical nature – peptide

34. Functions:
-activates hyaluronidase which decomposes hyaluronic acid in the membranes of kidney canaliculi – increases the reabsorption of water in kidneys;
-contractions arterioles and capillaries – increases blood pressure
Insufficiency – diabetes insipidus (polyuria, low density of urine, dehydratation)

35. Oxytocin
Chemical nature – peptide

36. Functions:
-stimulates the contraction of smooth muscles (of uterus during labor)
stimulates milk secretion (contraction of muscle fibers around mammary alveoli)
Using:
-for labor stimulation;
-to stop after labor hemorrhage;
-for stimulation of milk secretion

37. EPIPHYSIS (PINEAL GLAND)
Produces:
Мelatonin from serotonin (regulates the pigment metabolism)
Adrenoglomerulotro-pin – stimulates secretion of mineralocorticoids in the epinephrine glands cortex.
Inhibitor of gonadotropin – inhibits the synthesis of prolactin, cholesterol

38. PANCREAS Exocrine and endocrine parts
Endocrine – Langerhans islets (alpha-, beta- and delta-cells)

39. Alpha-cells: glucagon
Beta-cells: insulin
Delta-cells: somatostatin
Epithelium of ducts: lipocain

40. Insulin Nature – protein (51 АA)
Is formed from proinsulin by proteolisis
Contains zinc

41. Regulation of the synthesis:
Glucose concentration in blood
Other hormones (somatostatin)
Sympathetic and parasympathetic nervous system
It is destroyed by insulinase (enzyme of liver)
Target cells:
Hepatocytes
Myocytes
Adipocytes
In the unsufficiency – diabetes mellitus

42. The effect on carbohydrate metabolism
Increases the permeability of membranes for glucose
Activates glucokinase (hexokinase) in glycolysis
Activates TAC (citrate synthase)
Activates PPC (G-6-PDH)
Activates glycogen synthase
Activates pyruvate- and alpha-кetoglutarate dehydrogenase
Inhibits gluconeogenesis
Inhibits the decomposition of glycogen (glucose-6-phosphatase)

43. Effect on the protein metabolism
Increases the permeability of membranes for AA
Activates synthesis of proteins and nucleic acids
Inhibits gluconeogenesis
Effect on the lipid metabolism
Activates of the lipids synthesis
Promotes the saving of fats activating the decomposition of carbohydrates
Effect on the mineral metabolism
Activates Na/K-АТP-аse

44. Glucagon Nature – polypeptide Antagonist of insulin
Synthesis is activated in fasting

45. Functions Activates the decomposition of glycogen in liver
Activates gluconeogenesis
Inhibits glycolysis
Activates lipolysis

46. Somatostatin Nature – peptide Functions:
Inhibits secretion of insulin and glucagon
Inhibits secretion of STH and TTH
Inhibits secretion of local hormones of intestine

47. Lipocain Functions: Activates the synthesis of phospholipids in liver
Stimulates the action of lipotropic factors
Activates the oxidation of fatty acids in liver

48. THYROID GLAND Hormones of two types:
1. Iodine containing : thyroxin (tetraiodthyronin) and triiodthyronin – derivatives of tyrosine;
2. Calcitonin - peptide 48

49. Synthesis of iodine containing hormones is regulated by thyrotropic hormone, which in turn is stimulated by thyroliberin 49

50. Functions of iodine containing hormones
Necessary for normal growth, differentiation, sex and mental development
Regulate the speed of metabolism 50

51. Effect on protein metabolism Effect on carbohydrate metabolism
In physiological concentration stimulate synthesis of proteins, nucleic acids.
In the increased concentration activate the protein decomposition.
Effect on carbohydrate metabolism
Accelerate the absorption of carbohydrates in the intestine
Activate the decomposition of glycogen. 51

52. Effect on lipid metabolism Effect on energetic metabolism
Activate the exit of lipids from depot, its decomposition and oxidation
Effect on energetic metabolism
In excess thyroxin uncouples respiration and phosphorilation, decreases the ATP formation and increases the heat formation 52

53. Hyperfunction of gland – diffuse toxic goiter (thyrotoxicosis, Graves disease)
Goiter – hyperplasia of gland
Hypermetabolism
Increase of body temperature
Sweating, muscle weakness
Weight loss with good appetite
Tremor, emotional lability, insomnia
Exophtalm 53

54. Hypofunction of gland (occurs in the deficit of iodine in water, soil, air)
Decrease of metabolism
Decrease of body temperature
Hypofunction in childhood - cretinism
Growth inhibition
Unproportional body development
Disorders of mental development
Hypofunction in adults – mixedema
Edema of mucosa
mixedema
cretinism 54

55. Endemic goiter (occurs in the deficit of iodine in water, soil and air)
Connective tissue is enlarged in gland and it is increased in size markedly 55

56. Calcitonin Is synthesized by parafollicular cells of thyroid gland
Affects the metabolism of Са and Р
Promotes the transferring of Са2+ from blood into bones
Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine) 56

57. Increase of calcitonin hypocalciemia hypophosphatemia
hyperphosphaturia
Decrease of calcitonin
- hypercalciemia
hyperphosphatemia
hypophosphaturia 57

58. PARATHYROID GLANDS Parathyroid hormone - protein
Affects the metabolism of Са and Р
Promotes moving of Са2+ from bones into blood
Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine)
Stimulates the absorption of Ca in the intestine
Дія зв’язана з вітаміном D (утворює активну форму вітаміну D в нирках) 58

59. Hyperfunction (Recklinghausen’s disease)
Hypofunction
hypocalciemia
hyperphosphatemia
hypophosphaturia
tetanus
Hyperfunction (Recklinghausen’s disease)
hypercalciemia
hypophosphatemia
hyperphosphaturia
osteoporosis
Accumulation of Са in tissues 59

60. EPINEPHRINE GLANDS
Two parts:
-cortex
-medulla 60

61. Hormones of medulla - catecholamines
Epinephrine, norepinephrine and DOPA
Nature – derivatives of tyrosine
Excretion is regulated by sympathetic nervous system and brain cortex 61

62. Functions:
Stress hormones. Contraction of vessels, increase the blood pressure, accelerate pulse. Contraction of uterus muscles. Epinephrine relaxes the muscles of bronchi and intestine.
On carbohydrate metabolism:
-activates the decomposition of glycogen in liver and muscles
-activates glycolysis, PPC, TAC and tissue respiration
On protein metabolism
-accelerate the decomposition of proteins
On lipid metabolism
-activates lipase, mobilization of lipids and their oxidation 62

63. Hormones of cortex - corticosteroids
There are more than 50 corticosteroids
Nature – steroids
Are synthesized from cholesterol
Two groups
-glucocorticoids (protein, carbohydrate and lipid metabolism)
-mineralocorticoids (mineral metabolism) 63

64. Glucocorticoids Most important: corticosteron, cortison, hydrocortison
Synthesis is regulated by ACTH
Are transported combined with proteins
Half-life time – till 1 hour
In the decomposition17-ketosteroids are formed (excretion with urine). Diagnostic significance – index of the function of cortex of epinephrine glands and testis 64

65. 65

66. Functions Antiinflammatory, antiallergic, antiimmune Adaptive effect
Maintain the blood pressure
Maintain the volume of extracellular liquid 66

67. Effect on protein metabolism
Stimulate catabolic processes in connective, lymphoid and muscle tissues
Activate protein synthesis in liver
Stimulate amino transferases
Stimulate the urine biosynthesis 67

68. Effect on the carbohydrate metabolism Effect on the lipid metabolism
Increase the glucose level
Activate gluconeogenesis
Inhibit hexokinase (glycolisis)
Effect on the lipid metabolism
Activate lipolysis
Activate the conversion of FA into carbs 68

69. Mineralocorticoids Functions:
The most important hormone: aldosteron
Excretion is controlled by rhenin-angiothensin system
Functions:
-activate the reabsorption of Na, water and Cl in kidney canaliculi
- Promotes the excretion of К ions via the kidneys, skin and saliva 69

70. Disorders of the function of epinephrine gland cortex
Insufficiency: Addison disease (bronze disease)
Causes:
-injury of epinephrine gland cortex
-insufficient production of ACTH
Blood pressure decrease, loss of weight, weakness, anorexia.
Hyperpigmentation - bronze skin 70

71. Hyperproduction: Kushing syndrom
Causes: hypeplasia or tumor of epinephrine gland cortex
Obesity, particularly of the trunk and face (“moon face“) with sparing of the limbs; striae (stretches of the skin)
Proximal muscle weakness
Hirsutism (facial male-pattern hair growth)
Insomnia, impotence, amenorrhoea, infertility
Heart diseases, hypertension
Polyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes)
Kidney bones
Depression, anxiety
Hyperpigmentation 71

72. Aldosterone hyperproduction
Causes:
-aldosteroma
Symptoms:
-hypokaliemia
-hypernatriemia
-hyperchloremia
-hypervolemia
-edema, hypertension 72

73. Sex hormones Are synthesized in: -sex glands -placenta
-cortex of epinephrine glands
A little amount of female sex hormones is formed in male organism and vice versa.
Female – estrogens, progesteron.
Male – androgens. 73

74. Estrogens Nature: steroids
Estradiol – is formed in follicles of ovarium
Estron and estriol – are formed in liver and placenta in the metabolism of estradiol
естріол
eстрадіол 74

75. Functions of estrogens Biochemical functions of estrogens
Development of the female reproductive system organs
Ability to fertility in reproductive period
Biochemical functions of estrogens
Anabolic action on the tissues of reproductive organs
Inhibit the exit of Ca from bones (osteoporosis in menopause) 75

76. Progesteron Nature: steroid
Is formed in corpus luteum, placenta and epinephrine glands 76

77. Functions of progesteron
Prepares the endometrium of uterus to implantation of ovum
Inhibits the uterus contraction during pregnancy
Stimulates the growth of mammary glands 77

78. Androgens Testosteron Nature: steroid
Is formed in the interstitial cells of testis
Is excreted as 17-кetosteroids 78

79. Functions of testosterone Biochemical functions of testosterone
Development of the primary sex features
Development of the secondary sex features
Stimulates spermatogenesis
Biochemical functions of testosterone
Strong anabolic action (stimulates the synthesis of NA, proteins, phospholipids) – increases the mass of muscles
Keeps the Ca and P in organism 79

80. Derivatives of androgens – active anabolics80