Receptors Functions and Signal Transduction L1- L2

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Receptors Functions and Signal Transduction L1- L2 Faisal I. Mohammed, MD, PhD University of Jordan 1

Introduction to Physiology (0501110) Spring 2013 Subject Receptors: types and adaptation - Membrane or intracellular - Ion channels - G-protein - Enzyme linked - Intracellular - Second messengers - camp and cgmp, Phospholipid - Calcium calmodulin and IRS Lecture No. Lecturer Pages in the 11 th edition. textbook Pages in the 12 th edition textbook 1-2 Dr. Faisal 910-915 886-891 Signal Transduction (Regulation of cellular machinery) Extracellular regulators: nervous, endocrine, paracrine and autocrine Steroids: Their Signal Transduction And Mechanism Of Action 3-4 Dr. Faisal 934-936 962-963 5 Dr. Faisal 949 954 910-912 940-941 926-927 931 Textbook: Guyton Medical Textbook of Physiology By: Guyton and Hall 12 th edition

Objectives Define first messenger (Hormones) List hormone types Describe receptor types Outline the hormone receptors interactions Describe second messenger mechanism of action List second messengers University of Jordan 3

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Intercellular Communication Endocrine Cell Hormone Blood Target Cell Hormone Neuroendocrine Neuron Hormone Blood Target Cell Hormone Paracrine Cell Interstitial Fluid Target Cell Hormone Hormone Autocrine Cell Hormone Interstitial Fluid

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GAS MOLECULE University of Jordan 9

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Endocrine Glands and Hormones Neurohormone: Specialized neurons that secrete chemicals into the blood rather than synaptic cleft. Chemical secreted is called neurohormone. Hormones: Affect metabolism of target organs. Help regulate total body metabolism, growth, and reproduction. University of Jordan 13

Classes of Hormones Peptide and Protein Hormones (amino acid chain) Steroid Hormones (derived from chlesterol) Amine Hormones (derived from amino acid e.g tyrosin) Gas Nitric Oxide (NO) University of Jordan 14

Hormone types Circulating circulate in blood throughout body Local hormones act locally Paracrine act on neighboring cells Autocrine act on the same cell that secreted them University of Jordan 15

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Chemical classes of hormones Lipid-soluble hormones- use transport proteins in the plasma Steroid: Lipids derived from cholesterol. Are lipophilic hormones. Testosterone. Estradiol. Cortisol. Progesterone. Thyroid ( amine but lipid soluble) Nitric oxide (NO) University of Jordan 17

Chemical classes of hormones cont Water-soluble circulate in free form in the plasma Amines: Hormones derived from tyrosine and tryptophan. Polypeptides and proteins: Polypeptides: Chains of < 100 amino acids in length. ADH. Protein hormones: Polypeptide chains with > 100 amino acids. Growth hormone. Eicosanoid (prostaglandins) derived from arachidonic acid (20 carbon 4 double bonds) University of Jordan 18

Chemical Classification of Hormones cont Glycoproteins: Long polypeptides (>100) bound to 1 or more carbohydrate (CHO) groups. FSH and LH, TSH and hcg (human chorionic gonadotropin) They have α and β subunits (α is common and β is specific) Hormones can also be divided into: Polar: H 2 0 soluble. Nonpolar (lipophilic): H 2 0 insoluble. Can gain entry into target cells. Steroid hormones and T 4 (thyroxine tetraiodothyronine)) University of Jordan 19

Prohormones and Prehormones Prohormone: Precursor is a longer chained polypeptide that is cut and spliced together to make the hormone. Proinsulin gives insulin Preprohormone: Prohormone derived from larger precursor molecule. Preproinsulin. Prehormone: Molecules secreted by endocrine glands that are inactive until changed into hormones by target cells. T 4 converted to T 3 (tri-iodothyronin). University of Jordan 20

Peptide & Protein Hormones Gland/Tissue Hormones Gland/Tissue Hormones Hypothalamus TRH, GnRH, CRH Placenta HCG, HCS or HPL GHRH, Somatostatin, Anterior pituitary ACTH, TSH, FSH, LH, PRL, GH Kidney Renin Posterior pituitary Oxytocin, ADH Heart ANP Thyroid Pancreas Calcitonin Insulin,Glucagon, Somatostatin G.I. tract Gastrin, CCK, Secretin, GIP, Somatostatin Liver Somatomedin C (IGF-1) Adipocyte Leptin Parathyroid PTH Adrenal medulla Norepinephrine, epinephrine University of Jordan 21

Synthesis and secretion of peptide hormones University of Jordan 22

Amine Hormones Gland/Tissue Hypothalamus Hormones Dopamine Thyroid T 3, T 4 Adrenal medulla Epinephrine and Norepinephrine (NE, EPI) University of Jordan 23

Synthesis of Amine Hormones tyrosine hydroxylase dopa decarboxylase L-Dopa Tyrosine Dopaminergic Neurons Dopamine dopamine - hydroxylase Adrenergic Neurons Norepinephrine phenylethanolamine- N-methyltransferase Epinephrine Adrenal Glands Thyroid Hormones Thyroid Gland

Steroid Hormones Adrenal Cortex Testes Gland/Tissue Hormones Cortisol, Aldosterone, Androgens Testosterone Ovaries Corpus Luteum Estrogens, Progesterone Estrogens, Progesterone Placenta Kidney Estrogens, Progesterone 1,25-Dihydroxycholecalciferol (calcitriol) University of Jordan 25