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ThemeTheme: : Hormones as Hormones as biological regulators. biological regulators. General mechanismsGeneral mechanismsof hormones action.of hormones action.
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) enters 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:
Functions of hormones.
Hormones regulate the following processes: 1. Metabolic pathways Metabolic regulation
requires rapidly acting mechanisms. Many of the hormones involved therefore regulate interconversion of enzymes (glycogen, fat).
2. Digestive processes Digestive processes are usually regulated by locally acting peptides (paracrine).
3. Maintenance of ion concentrations (homeostasis). Concentrations of Na+, K+, and Cl– in body fluids, and the physiological variables dependent on these (e. g. blood pressure), are subject to strict regulation.
Classification of hormones
hormones of protein structure: all hormones of anterior pituitary (except ACTH), insulin, parathyroid hormone;
hormones of peptide structure: ACTH, calcitonin, glucagon,hormones of posterior pituitary, factors of hypothalamus, thymozin;
steroid hormones: adrenal cortical steroids, sex hormones;
hormones - derivatives of amino acid: thyroid hormones, adrenal medulla hormones, epiphysis hormones;
hormones derivatives of unsaturated fatty acid: prostaglandins.
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 hormonesProstaglandins, peptides Vitamin D, steroids Thyroid hormones
Second messenger
Activated protein kinase
Phosphorilated proteins
Biological action
Protein synthesis
NUCLEUS
m-RNA
Mechanism of water soluble hormones action (not permeating into the cells):
Hormone (epinephrine, glucagon, ACTH, LH, FSH, TSH, parathyroid hormone, calcitonin) arriving at the surface of the cell becomes bound to the specific receptor sites on the outer surface of the cell membranes. Its binding is believed to cause a local conformational change in the membrane resulting in the activation of adenylate cyclase, located on the inner surface of the cell membrane. The active form of adenylate cyclase converts ATP into cyclic AMP. The cyclic AMP so formed then binds to the regulatory subunit of protein kinase, releasing its catalytic subunit in an active form.
Mechanism of steroid hormones action (permeating into the cells):
• In difference to hormones of protein and peptide nature, receptors for steroid hormones are located within the cells - in the cytoplasm. From cytoplasm the hormone-receptor complexes is translocated into the nucleus where they interact with DNA of nuclear chromatin causing the activation of genes for respective enzyme proteins.
• So, if hormones of the first group cause the activation of existing enzyme molecules, the acting on the target cells of steroids and thyroid hormones results in the biosynthesis of new enzyme molecules.
Hypothalamus
3 peptides are synthesized and migrate along axons into posterior lobe of pituitary
1) Antidiuretic hormone (vasopressin)
2) Oxytocin3) Neurophysin (promotes
transport of vasopressin and oxytocin into pituitary gland)
Two groups of hormones are produced by hypothalamus corresponding to the anterior and posterior pituitary.
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.
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 fatThe 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: -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)
Oxytocin
Chemical nature – peptide
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) Adrenoglomerulotr
o-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 PPP (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 glycolysis
Activates lipolysis
The eicosanoids are a group of signaling substances that arise from the C-20 fatty acidarachidonic acid and therefore usually contain20 C atoms (Greek eicosa = 20). As mediators,they influence a large number of physiologicalprocesses. Eicosanoid metabolismis therefore an important drug target. Asshort-lived substances, eicosanoids only actin the vicinity of their site of synthesis (paracrineeffect).