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Hormones : Outline Chemistry and Functions INTRODUCTION Hormones are chemicals produced by ductless glands and are transported by blood to target tissues to produce inhibiting or simulatory effect in these tissues . Hormones are synthesized in the body unlike vitamins . The role of hormones is to provide communications between cells to regulate their development and coordinate various cellular activities . Since the communication among cells is done by hormones , they are mcalled chemical messengers . Hormones present in the blood are bound to plasma protein fractions and transported along with them . For example thyroxine and corticosteroids are bound to globulin , estrogens and androgens are bound to albumin . Hormones are substances synthesized in the body in small quantities but have a profound biochemical effect in the control and regulation of metabolic events and contribute in some cases to intercellular and intracellular communication . Functions of hormones cover four major areas namely: a. re-production, (b) growth and development (c) maintenance of inter-nal environment, and (d) energy production, utilization and storage. *Derangement of the endocrine balance either due to hypo or hypo results in metabolic aberrations or syndromes. *Some are synergistic others are antagonistic. *Present in minute amounts and act at very low concentration. Similarities with enzymes 1.They act as body catalysts resembling enzymes in many respects. 2.They are required only in small quantities. 3.They are not used up in reactions. Differences from enzymes 1.They are produced in an organ other than the target tissues. 2.They are secreted in blood prior to use. Thus the target levels of hormones can give some indication of endocrine gland activity and target organ exposure. 3.While all enzymes are proteins, only some hormones are pro-teins, a few are peptides, Some hormones are derived from amino acids while some are steroids in nature. Hormones Secretion Hormones are secreted by specialized cells known as glands. Hormones are recognized by special called receptors located on the cell surface of the target cells. On receiving a chemical signal with the help of a hormone, the receptors trigger a cell response by bringing about particular changes in the proper-ties of the cells. The secretion of hormones is controlled by the anterior lobe of the pituitary gland. This gland is located at the base of the brain. These pituitary hormones are transported to other glands, such as adrenal cortex, thyroid, and sex glands, etc. to stimulate the production of other hormones. Hormones are highly potent and so are produced in small quantities. Hormones Secreting Glands Major hormone secreting glands are: 1.Pituitary 2.Thyroid 3.Parathyroid 4.Adrenal 5.Pancreas 6.Ovaries 7.Testes Classification of Hormones Hormones do not have any special structural feature in common. Chemically they belong to different classes of compounds. Based on their Chemical Structure Hormones can be classified into the following three major classes namely steroids, polypeptides and amino acid derivatives. 1.Steroid hormones: For example adrenocorticosteriod hormones, androgens, estrogens and progesterone. 2.Peptide protein hormones: For example, Insulin, glucagon, parathormone, calcitonin, pituitary hormones. 3.Amine hormones: These are derived from amino acid tyrosine. For example, epinephrine, norepinephrine and thyroid hor-mones. Based on the Mode of Action 1.Hormones which act by binding to their receptors on the plasma membrane, e.g. insulin. 2.Hormones which act through the second messenger, cAMP, for example, glucagon. 3.Hormones which bind to high affinity receptor proteins in the cytosol move to the nucleous as a complex, interact with chro-matin there, increases the production of mRNA and thereby proteins, for example, steroids. 4.Hormones which straight away move to the nucleus and increase with specific receptor proteins in the nucleus and increase transcription and translation, for example, triiodo-thyrosine(T3). 5. Hormones which increase the extent of transolation without increasing transcription for example, insulin, ACTH (Adreno-corticotropic hormone). Factors Regulating Hormones Action Action of a hormone at a target organ is regulated by four factors: 1.Rate of synthesis and secretion of hormones. 2.In some cases specific transport systems in plasma. 3.Hormone-specific receptors in target cell membranes which differ from tissue to tissue. oikidneys. Mode of Action of Hormones 1. Induction of enzyme synthesis at the nuclear level , for example thyroxine steroid hormones . 2. Some hormones do not influence transcription , i.e. mRAN production . 3. Some hormones act at level of the bio-membranes first . They may have no activity in membrane free preparation. 4. Many hormones will be functionless if cAMP does not serve them , hence cAMP is called the messenger of those hormones which are themselves first messengers . 5. Action through calcium . Many hormones discharges its function through calcium . STEROID HORMONES Steroid hormones are those which have a steroid nucleus . The steroid nucleus has a four ring network , consisting of three cyclohyexane ring and one cycleopentane ring joined in a particular manner . In addition to hormones , the steroid is also present in some vitamins , drugs and bile acids . CH3 CH3 CH3 CH3 CH3 HO Steroid Nucleus Cholesterol If an alcoholic hydroxyl group is present in the steroid it is knows as sterol .Cholesterol is the most common sterol present in animals . Sex Hormones Sex hormones are the important steroid hormones . In males , steroid hormones are synthesized in the testes and the adrenal cortex . Testosterone , dihydrotesterone and androgens are the male sex hormones . During puberty , these stimulate the development of male sex characteristics . ism primarily in ovaries . Female sex hormones are responsible for the development of female sex characteristics during puberty . Some other steroids such as cortisone , corticosterone and aldosterone affect metabolism , minerals and water balances . The deficiency of these hormones leads to loss of fluids, while an excess of these hormones causes an increase in blood pressure . Androgens and oestrogens have significant affect on the anabolic systems . Androgens and oestrogens are abused by athletes , weight – lifters and other sports persons to increase muscle mass and strength . Such uses of anabolic steroids is now banned in competitive sports. Some female sex hormones which are synthesized on a large scale are used as oral contraceptives. OH CH3 OH OH CH3 HO CH3 Esteriol Testosterone Androgens Biochemical Effects 1. Influence protein metabolism . Anabolic effect on protein conservation and retention of nitrogen and thereby muscle growth and maintenance of muscle mass . 2. Mineral metabolism 3. Carbohydrate metabolism 4. Citric acid cycle and fatty acid synthesis are stimulated by androgens. Oestrogens Ovarian hormones produced by the graafian follicles of the ovary . Responsible for the regulation of menstrual cycle as well as reproductive cycle . Biochemical Effects Oestrogen stimulates the development, maturation and function of the female sex organs and thereby the secondary sex characteristics: 1. Proliferation of vaginal epithelium, endometrium. 2. Increase secretion of mucus by the cervical glands. 3. Growth of uterine tissue and mammary gland . 4. Reduces hyperlipidaemia, hypercholesterolaemia, prevent atherosclerosis. 5.Oestrogen administration elevates calcium and phosphorus. Progesterone Secreted by corpus lentium during the later half of the menstrual cycle . Development of mammary luster and maintenance of uterus during gestation period . Insulin Insulin is a protein hormones , secreted by the β – cells of the Islets of Langerhans of pancreas . It has been isolated and prepared in the crystalline form . Crystalline insulin contains Zn . It has a molecular weight of 5734 . Insulin molecular is compound of two polypeptide chains the glycyl or 'A' chain and phenylalanine or β chain containing a total of 51 amino acids . The glycyl chain is acidic and contains 21 amino acids. The phenylalanine chain is basic and contains 30 amino acids . Both the chains are held together by disulphide bridges . The target tissues of insulin are the muscles , liver , adipose tissue and heart . Insulin circulates in blood mostly along with β- and – globulin of plasma protein. The normal concentration of plasma insulin is 30 in µu per liter . Insulin promote the entry of glucose in all tissues of the body except liver . Metabolic Action of Insulin 1. Lower of blood glucose level 2. Increase in the rate of oxidation of glucose in tissues. 3. Increase glycogen formation in the liver and muscles. 4. Depressing gluconeogenesis 5. Accelerating the rate of conversion of glucose to fat (lipogenesis ) 6. Depressing ketogenesis. 7. Increasing protein synthesis . Insulin is administered parenterally to reduce hyperglycema in diabetes mellitus. It brings down blood glucose level by increase the oxidation of glucose and promoting glycogenesisin liver and muscles . Insulin Deficiency : Diabetes Mellitus -Due to inadequate insulin production - Insulin not binding to the receptors - Accelerated insulin destruction - Insulin inhibitors and antagonists Diabetes Mellitus – Two Types - Real deficiency or shortage of insulin in the circulating plasma. - Because of resistance to the hormone due to lack of receptors or their decreased number in proportion to body size. 90% - NIDDM ( Non- insulin dependent diabetes mellitus, Type II) 10% - Juvenile IDDM ( Insulin dependent diabetes mellitus, Type I) Type ll No injection – by diet / oral hypoglycaemic drugs enhance the action of receptor. Type l Injection of insulin . Glucagon Glucagon is a hyperglycemic, glycogenolytic hormone. It is secreted by the α cells of the islets of Langerhans in pancreas . It is a proteins consisting of a straight polypeptide chain, which contains, 29 amino acid residues. It has a MW of 3485 . Glucagon is very active when administered and has an effect opposite to that insulin. The blood sugar rises immediately, reaches a peak in about 30 minutes and returns to the original level in one hour. AMINE HORMONES These are water soluble compounds having an amino group, e.g. adrenaline ( epinephrine ) and thyroid hormones. Adrenaline Adrenaline is needed to prepare people for emergency in several ways. Adrenaline increase the rate of heart beat , the heart output and blood pressure and thus prepares the cardiovascular system for emergency section . It stimulates the breakdown of liver glycogen into blood glucose which is the fuel for anaerobic muscular work. These properties make adrenaline one of the most valuable drugs.