Mechanism of hormone action

Transcription

1 Mechanism of hormone action ผศ.ดร.พญ.ส ว ฒณ ค ปต ว ฒ ภาคว ชาสร รว ทยา คณะแพทยศาสตร ศ ร ราชพยาบาล Aims What is hormone receptor Type of hormone receptors - cell surface receptor - intracellular receptor Signaling via hormone receptors Type of second messengers 1

2 Hormone receptor A protein of target cells that binds to a specific hormone Target cells: Any cells that have specific receptor for hormone Hormone and target cells specificity H + R Specificity Affinity Number Reversible HR complex Single H + Different R Different Effects 2

3 Hormone action One hormone Multiple actions Angiotensin II Blood pressure Aldosterone Gene expression Signal transduciton One actions Glucose utilization Multiple hormones There are 2 groups of hormone receptors Cell-surface receptors olypeptide hormones: GH, Insulin, GnRH, Gn Catecholamines: E, NE Intracellular receptors Steroid hormone Thyroid Hormone 3

4 Cell-surface receptors Glycoprotein that cross the cell membrane to create extracellular and intracellular domains. Extracellular domain Intracellular domain Cell-surface receptors G-protein coupled receptor Receptor regulating ion channels Receptor associated tyrosine kinase Receptor containing tyrosine kinase 4

5 Cell-surface receptors G-protein coupled receptor Extracellular Receptor containing tyrosine kinase Receptor associated tyrosine kinase Cytoplasmic TH,LH, Glucagon Receptor Receptor regulating ion channels Insulin Receptor β-adrenergic Receptor GH Receptor Three stages of cell signaling Hormone recognition (1 st messenger) Signal generation (2 nd messenger) Alteration of intracellular processes 5

6 G protein couple receptor G protein couple receptor G protein α subunit Stimulator bind to GD β, γ subunits Inhibitor Adrenergic Adenylyl cyclase LC Ion channels G protein couple receptor G protein couple receptor Movie Hormone action mov 6

7 Type of G alpha subunits - Adenylyl cyclase αi + αs + αq + α 12,13 Adenylyl cyclase LC Rho Second Messengers Second Messengers Chemical signal which connect to other protein to co-ordinate the activities of other molecule G protein second messengers Enzyme Adenylyl cyclase Guanylyl cyclase cam cgm hospholipase C hospholipase A2 Ion channels I 3, DAG Arachidonic acids Ca 2+ 2nd messenger 2nd messenger 7

8 Second Messengers Second Messengers Amplification signals Amplification signals Cellular responses Cellular responses Signalamiplification.swf cgm Second Messenger Guanylate cyclase cgm 8

9 Action of epinephrine on liver cell Action of epinephrine on liver cell hospholipase C hospholipase C C hospholipase A 2 Arachidonic acid -G -TX - Leu 9

10 Receptor containing tyrosine kinase Insulin Receptor Receptor auto-phosphorylation Receptor Associated with Tyrosine Kinase GH Receptor lasma membrane GH GH GH GH IGF JAK2 JAK2 mrna mrna JAK 2 = Janus kinase (cytoplasmic tyrosine kinase) STAT = Signal transducer and activators of transcription 10

11 Intracellular Receptors NH 2 Interact with other transcription factors DNA binding domain Hormone binding COOH Steroid Receptors rogesterone Glucocorticoid Estrogen Thyroid hormone Receptors NH 2 A/B C D E F COOH DNA Hormone Binding Intracellular receptor model Cytoplasmic receptor-thyroid H, vit D, aldosterone 11

12 Steroid hormone action athway I: ER, R, GR, AR HRE GTF Basal Gene HRE GTF Stimulated Gene Hormone Co-activator Hormone receptor GTF General transcription factors 12

13 athway II: thyroid hormone, vitamin D repressor HRE Gene HRE GTF Basal Gene GTF Stimulated HRE Co-repressor Gene RXR Hormone receptor Hormone Regulation of transcription by hormone not entering cells CREB = cam response element binding protein F = transcription factor = CREB- CRE = cam regulatory element = RNA polymerase cam CREB- CREB rotein kinase A Transcription Translation or 13

14 Two General Classes of Hormones Steroid hormones Slower eptide hormones Faster Termination of hormone action eptide hormones Hormones are degrade by blood enzymes lasma membrane-hormone-receptor complex was internalized by endocytosis and degraded by lysosomal enzymes Steroid hormones In the absence of further stimulation, newly synthesized RNA and proteins are degraded by cytoplasmic enzyme actions 14

15 ractice Questions Which of the following is a steroid hormone? A. Insulin B. Testosterone C. Epinephrine D. Oxytocin E. Growth hormone Ans: : B 15

16 The transcription of new messenger RNA is a function of A. steroid hormones. B. amino acid-based hormones. C. pancreatic hormones. D. catecholamines. E. pituitary gland hormones. Ans: : A 16