Chapter-13 Hormones and Signal Transduction Page 396-401 Dr. Amjid Iqbal PhD (University of 1
Living things coordinate their activities through biochemical signaling system Intercellular signals are mediated by chemical messengers known as hormones. 2
The Endocrine Glands are the organs of the Endocrine System. They produce and secrete (release) Hormones. They are located all over your body. 3
The answer is Hormones! 4
Hormones In higher animals, specialized ductless endocrine glands synthesize endocrine hormones, that are released into blood stream in response to external stimuli. These hormones carried to target cells, in which they show response 5
Functions of hormones Maintain homeostasis (a steady state, e.g insulin and glucagon maintain blood glucose level) Respond to wide variety of external stimuli (preparation for flight or fight) Follow various cyclic and developmental program (sex hormones regulate sexual differentiation, maturation etc etc) 6
Nature and response to hormones Most hormones are either polypeptides, amino acid derivatives or steroids. Only those cells with specific receptor for given hormone will respond to the presence of hormone Secretion of many hormones is under feedback control The concentration of circulating hormones are measured using radioimmunoassay 7
response endocrine cell hormones receptor protein target cell 8
Hormones only work on certain cells, called target cells. The target cells have special receptors that recognize the hormones and allow them to influence that cell. Target Cell for Hormone A Target Cell for Hormones A and B Target Cell for Hormone B Hormone A Hormone B These receptors recognize the hormones. They fit like a lock and key. 9
Stimulus: You hear a loud noise A large dog runs toward you, growling and barking You eat a large candy bar You have not eaten in six hours You have strep throat 10
A chain of events occur that lead from the stimulus to the response. 11
Focus of different hormones in this Chapter Pancreatic Islet Hormones Epinephrine and Norepinephrine Steroid hormones Growth hormone 12
Pancreatic Islet Hormones Control Fuel Metabolism Pancreas is large glandular organ, bulk of which is exocrine gland and produce digestive enzymes, like trypsin, chymotrypsin, Rnase A, α-amylase and phospholipase A2. 1-2% of pancreatic tissues consists of scattered clumps of cells known as islets of Langerhans, which comprise endocrine gland and maintain energy homeostasis. 13
Pancreatic islets Pancreatic islets contain three types of cells, each secretes a polypeptide hormone α-cells secrete glucagon (29 residues) β-cells secrete insulin (51 residues) δ-cells secrete somatostatin (14 residues) 14
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Insulin Insulin, secreted in response to high blood glucose level. Stimulate muscle, liver and adipose cells to store glucose for later use by synthesizing glycogen, protein and fat. 16
You eat. Glucose (sugar) in the blood increases. Increased glucose is detected by receptors that notify the brain. It sends a message to the pancreas to produce insulin. Pancreas stops making insulin. Blood glucose level drops as it is removed by the cells. Insulin tells muscle and liver to take up glucose from the bloodstream and use it for energy or store it for later. Brain reduces appetite. 17
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Glucagon Secreted in response to low blood glucose Stimulate the liver to release glucose through break down of glycogen (glycogenolysis) and synthesis of glucose (gluconeogenesis). It also stimulate the adipose tissue to release fatty acids through lipolysis Somatostatin, secreted by hypothalamus, inhibit the release of insulin and glucagon 19
Release of Hormones Polypeptide hormones are ribosomally synthesized as prohormones, processed in rough endoplasmic reticulum and Golgi apparatus for form mature hormone and then packaged in secretary granules to await signal for their release by exocytosis 20
Most potent physiological stimuli for the release of insulin and glucagon are high and low blood glucose concentration. Release of hormones is also influenced by autonomic nervous system and hormones secreted by gastrointestinal tract. 21
Epinephrine and Norepinephrine prepare the body for action Adrenal glands consist of medulla (core) and glandular cortex (outer layer) Adrenal medulla synthesize two hormonally active catecholamine (amine derivative of catechol): Norepinephrine (noradrenalin) and epinephrine (adrenalin). These hormones are synthesized from tyrosine 22
Adrenal Gland 23
Adrenoreceptors Biological effects of catecholamines are mediated by two class of plasma membrane receptors α- and β-adrenergic receptors (also known as adrenoreceptors) Agonists: Substances that bind to a receptor so as to evoke a response Antagonists: Substances that bind to receptor but fail to elicit a response, therefore blocking agonist action. 24
β-adrenergic receptors are stimulated by isoproterenol but blocked by propranolol α-adrenergic receptors are blocked by phentolamine Both α-and β-adrenergic receptors, occur on separate tissues and respond differently to catecholamines. 25
β-adrenergic receptors It stimulate 1-Glycogenolysis and gluconeogenesis in liver, glycogenolysis in skeletal muscle 2-Lipolysis in adipose tissue 3-Relaxation of smooth muscles in the bronchi and in blood vessels supplying blood to skeletal muscles, 4-Increase heart action 26
α-adrenergic receptors 1-They stimulate smooth muscles contraction in blood vessels supplying peripheral organs like skin and kidney. 2-Smooth muscle relaxation in gastrointestinal tract and blood platelet aggregation. Mobilization of energy resources and their shunting to where they are most needed to prepare body for action 27
Therapeutic Consequences Tissue distribution of both receptors and their response to agonists and antagonists have therapeutic significance Propranolol is used to treat high blood pressure and protect against heart attack Epinephrine has bronchodilator effect and use in treatment of asthma (a breathing disorder caused by inappropriate contraction of bronchial smooth muscle) 28
Steroid hormones regulate a wide variety of metabolic and sexual processes Adrenal cortex produce at least 50 different adrenocortical steroids. They are of following types Glucocorticoids Mineralocorticoids Androgens and Estrogens 29
Glucocorticoids Glucocorticoids affect carbohydrate, protein and lipid metabolism in a manner opposite to that of insulin and influence vital functions including inflammatory reactions and capacity to cope with stress Most common glucocorticoid is cortisol (also known as hydrocortisone) a C21 compound. 30
Mineralocorticoids Mineralocorticoids function to regulate the excretion of salt and water by kidneys, and most common is aldosterone, a C21 compound. 31
Transportation of Steroids Steroids, being water insoluble are transported in blood in complex with glycoprotein transcortin and albumin The steroids pass through the membranes of their target cells to cytosol, where they bind to their steroid receptors. 32
The steroid-receptor complex migrate to cell nucleus, where they function as transcription factor, where they induce or repress transcription of specific genes In this way glucocorticoids and mineralocorticoids influence the expression of numerous metabolic enzymes in target tissues. 33
Gonadal Steroids mediate sexual development and function Gonads Testes in males and ovaries in females produce sperm and ova, also secrete steroid hormones (androgens and estrogens) that regulate sexual differentiation, expression of secondary sex characteristics Testes and ovaries produce both androgens and estrogens 34
Androgens--Male Sex hormone Testes predominantly produce androgens, which are known as male sex hormone. Testosterone is prototypic androgen, a C19 compound. Androgens play key role in sexual differentiation If gonads of an embryonic male are surgically removed, that individual will become phenotypic female 35
Mammals are programmed to develop as female unless embryonically subjected to the influence of testicular hormones Genetic males with absent or nonfunctional androgen receptors are also phenotypic female and such condition called testicular feminization 36
Androgens promote muscle growth and known as anabolic steroids Anabolic steroids used to enhance athletic performance, but their use can cause adverse effects like cardiovascular disease, development of breast tissue in males, masculinization in female, temporary infertility, stunted growth 37
Anabolic steroids are controlled substance and their use is banned to prevent unfair advantage over athletes not taking steroids. 38
Estrogens-Female Sex hormones Produce in overies, estrogens like β-estradiol are C18 compounds. Another class of ovarian steroids are progestins (C21 compounds) help to mediate menstrual cycle and pregnancy. 39
Growth hormone Binds to Receptors in Muscle, Bone and Cartilage Growth Hormone (GH), 191 residue polypeptide produced by pituitary gland. It stimulates growth and metabolism in muscle, bone and cartilage cells. Overproduction of GH is due to pituitary tumor, results in excessive growth 40
Gigantism Overproduction of GH, while skeleton is still growing, then this excessive growth is of normal proportion over the entire body, result in gigantism Excessive GH inhibits the testosteron production 41
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Acromegaly and Dwarfism If skeleton has already matured, GH stimulates the only the growth of soft tissues, resulting in enlarged hands and feet and thickened facial features, a condition called acromegaly. GH deficiency results in insufficient growth called dwarfism. This can be treated before sekelatal maturity by regular injection of human GH (hgh) 44
Acromegaly Hypersecretion of GH 7 ft 1 ¼ inches 45
Dwarfism Hyposecretion of GH Kenadie - worlds smallest girl due to primordial dwarfism Little People Big World 46
hgh can be synthesized via recombinant DNA techniques, its non medical use by athletes is prohibited. hgh has been taken by individuals to increase their athletic powers. But because of its adverse side effects, which include high blood pressure, joint and muscle pain and acromegaly and to eliminate unfair competitive advantage, its nonmedical use is prohibited. 47