GENERAL PRINCIPLES OF METABOLISM REGULATION. HORMONES.

GENERAL PRINCIPLES OF GENERAL PRINCIPLES OF METABOLISM REGULATIONMETABOLISM REGULATION. .

HORMONES.HORMONES.

Highest level – nervous system

Intermediate -hormonal regulation

Intracellular(enzymes)

Levels of the homeostasis regulation

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.

1. Hypothalamus2. Pituitary3. Epiphysis4. Thymus5. Thyroid gland6. Parathyroid glands7. Langergans’ islands of pancreas8. Epinephrine glands9. Sex glands

Endocrine glands:

Classification of hormones according to chemical

nature1. Proteins: hormones of anterior pituitary

(except ACTH), insulin, parathyroid hormone.2. Peptides: ACTH, calcitonin, glucagon,

vasopressin, oxytocin, hormones of hypothalamus (releasing factors and statins).

3. Derivatives of amino acids: catecholamins (epinephrine and norepinephrine), thyroxin, triiodthyronin, hormones of epiphysis.

4. Steroid (derivatives of cholesterol): hormones of the cortex of epinephrine lands, sex hormones.

5. Derivatives of polyunsaturated fatty (arachidonic) acids: prostaglandins.

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)

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

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

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

Inactivation of hormones

After biochemical effect hormones are released and metabolized

Hormones are inactivated mainly in liverInactive 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

1. Change the permeability of cell membrane, accelerate the penetration of substrates, enzymes, coenzymes into the cell and out of cell.

2. Acting on the allosteric centers affect the activity of enzymes (Hormones penetrating membranes).

3. Affect the activity of enzymes through the messengers (cAMP). (Hormones that can not penetrate the membrane).

4. Act on the genetic apparatus of the cell (nucleus, DNA) and promote the synthesis of enzymes (Steroid and thyroid hormones).

THE FINAL EFFECTS OF HORMONES ACTION

HYPOTHALAMUSIt 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.

Tight anatomical bonds with pituitary gland

Two groups of hormones related to anterior and posterior lobes of pituitary

Hypothalamus and posterior lobe of

pituitary

3 peptides are synthesized

Migrate along axons into posterior lobe of pituitary

1) Antidiuretic hormone (vasopressin)

2) Oxytocin3) Neurophysin (promotes

transport of vasopressina and oxytocin into pituitary gland)

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

•somatoliberin,•thyroliberin,•corticoliberin,•foliliberin,•prolactoliberin,•luteinising-hormone liberin, •melanoliberin

•somatostatin, •prolactostatin, •melanostatin

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.

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

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.

Acts both directly and through the stimulation of the formation of polypeptides somatomedins (insulin-like growth factors).

ILGF are synthesized in liver

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.

In the inherited hypoplasia of pituatary gland dwarfism is developed.

For the treatment GH is used.

Hyperproduction of GH before puberty and before the completion of ossification results in gigantism

Yao Defen, the tallest women

in the life, 2.36 м

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

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

Cushing’s diseaseCushing'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 weaknessHirsutism (facial male-pattern hair growth)Insomnia, impotence, amenorrhoea, infertilityHeart diseases, hypertensionPolyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes) Kidney bonesDepression, anxietyHyperpigmentation

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

Gonadotropic hormones

Chemical nature – protein (glycoprotein)

Secretion is stimulated by foliliberin Function: stimulates the function of follicles in women and spermatogenesis in men

Follicle-stimulating гормон

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

ProlactinChemical 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

Lipotropic hormonesChemical nature – simple proteins

Functions: -mobilization of lipids from depot;-melanocyte stimulating function;-decrease Ca in blood

THE INTERMEDIATE LOBE OF PITUITARY

Chemical nature – peptide

Functions: -stimulates melaninogenesis;-adaptation of vision in darkness

Melanocyte stimulating hormone (melanotropin)

POSTERIOR LOBE OF PITUITARY

Chemical nature – peptide

Vasopressin (antidiuretic hormone)

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

EPIPHYSIS (PINEAL GLAND) Produces: Мelatonin from serotonin (regulates

the pigment metabolism) Adrenoglomerulot

ro-pin – stimulates secretion of mineralocorticoids in the epinephrine glands cortex.

Inhibitor of gonadotropin – inhibits the synthesis of prolactin, cholesterol

PANCREAS Exocrine and endocrine parts

Endocrine – Langerhans islets (alpha-, beta- and delta-cells)

Alpha-cells: glucagonBeta-cells: insulinDelta-cells: somatostatinEpithelium of ducts: lipocain

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

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

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)

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•Inhibits gluconeogenesis

Effect on the mineral metabolism•Activates Na/K-АТP-аse

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

FunctionsActivates the

decomposition of glycogen in liver

Activates gluconeogenesis

Inhibits glycolysisActivates lipolysis

Somatostatin Nature – peptide

Functions:• Inhibits secretion of insulin and

glucagon• Inhibits secretion of STH and TTH• Inhibits secretion of local hormones

of intestine

Lipocain

Functions:• Activates the synthesis

of phospholipids in liver• Stimulates the action of

lipotropic factors • Activates the oxidation

of fatty acids in liver

THYROID GLAND

Hormones of two types:

1. Iodine containing : thyroxin (tetraiodthyronin) and triiodthyronin – derivatives of tyrosine;

2. Calcitonin - peptide

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

Functions of iodine containing hormones

Necessary for normal growth, differentiation, sex and mental development

Regulate the speed of metabolism

Effect on protein metabolismIn 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 intestineActivate the decomposition of glycogen.

Effect on lipid metabolismActivate the exit of lipids from depot, its decomposition and oxidation

Effect on energetic metabolismIn excess thyroxin uncouples respiration and phosphorilation, decreases the ATP formation and increases the heat formation

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

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

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

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)

Increase of calcitonin

- hypocalciemia- hypophosphatemia- hyperphosphaturia

Decrease of calcitonin- hypercalciemia- hyperphosphatemia- hypophosphaturia

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)

Hyperfunction (Recklinghausen’s disease)

- hypercalciemia- hypophosphatemia- hyperphosphaturia- osteoporosis- Accumulation of Са

in tissues

Hypofunction- hypocalciemia- hyperphosphate

mia- hypophosphaturia- tetanus

EPINEPHRINE GLANDS Two parts:

-cortex-medulla

Hormones of medulla - catecholamines

Epinephrine, norepinephrine and DOPA Nature – derivatives of tyrosine Excretion is regulated by sympathetic

nervous system and brain cortex

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

respirationOn protein metabolism-accelerate the decomposition of proteinsOn lipid metabolism-activates lipase, mobilization of lipids and their

oxidation

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)

Glucocorticoids

Most important: corticosteron, cortison, hydrocortison

Synthesis is regulated by ACTHAre transported combined with proteinsHalf-life time – till 1 hourIn the decomposition17-ketosteroids

are formed (excretion with urine). Diagnostic significance – index of the function of cortex of epinephrine glands and testis

Functions

• Antiinflammatory, antiallergic, antiimmune

• Adaptive effect• Maintain the blood pressure• Maintain the volume of extracellular

liquid

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

Effect on the carbohydrate metabolism

Increase the glucose level• Activate gluconeogenesis• Inhibit hexokinase (glycolisis)

Effect on the lipid metabolism

• Activate lipolysis• Activate the conversion of FA

into carbs

MineralocorticoidsThe most important hormone:

aldosteronExcretion is controlled by rhenin-

angiothensin systemFunctions:-activate the

reabsorption of Na, water and Cl in kidney canaliculi

- Promotes the excretion of К ions via the kidneys, skin and saliva

Disorders of the function of epinephrine gland

cortexInsufficiency: Addison disease

(bronze disease)Causes: -injury of epinephrine gland cortex-insufficient production of ACTHBlood pressure

decrease, loss of weight, weakness, anorexia.Hyperpigmentation - bronze skin

Hyperproduction: Kushing syndromCauses: hypeplasia or tumor of

epinephrine gland cortexObesity, particularly of the trunk and face (“moon face“) with sparing of the limbs; striae (stretches of the skin)Proximal muscle weaknessHirsutism (facial male-pattern hair growth)Insomnia, impotence, amenorrhoea, infertilityHeart diseases, hypertensionPolyuria, hypokalemia hyperglycemia, glucosuria (steroid diabetes) Kidney bonesDepression, anxietyHyperpigmentation

Aldosterone hyperproductionCauses: -aldosteroma

Symptoms:-hypokaliemia-hypernatriemia-hyperchloremia-hypervolemia-edema,

hypertension

A little amount of female sex hormones is formed in male organism and vice versa.

Female – estrogens, progesteron.

Male – androgens.

Sex hormones

Are synthesized in:-sex glands-placenta-cortex of epinephrine

glands

EstrogensNature: steroidsEstradiol – is formed in follicles of

ovariumEstron and estriol – are formed in liver

and placenta in the metabolism of estradiol

eстрадіол естріол

Functions of estrogensDevelopment 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)

Functions of progesteronPrepares the endometrium of uterus to implantation of ovumInhibits the uterus contraction during pregnancyStimulates the growth of mammary glands

Progesteron

Nature: steroidIs formed in corpus luteum, placenta and

epinephrine glands

AndrogensTestosteron

Nature: steroidIs formed in the interstitial cells of

testisIs excreted as 17-кetosteroids

Functions of testosteroneDevelopment of the primary sex

featuresDevelopment of the secondary sex

featuresStimulates 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