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Hormones Biochemical classification Mechanism of action Hierarchy

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Presentation on theme: "Hormones Biochemical classification Mechanism of action Hierarchy"— Presentation transcript:

1 Hormones Biochemical classification Mechanism of action Hierarchy
Feedback loops Signal transduction

2 Amino acid derivatives
Polypeptides Oxytocin thyrotropin ACTH Insulin glucagon somatotropin FSH LH vasopressin Steroids Aldosterone corticosterone Progesterone Estrogen testosterone cortisol Amino acid derivatives Epinephrine norepinephrine dopamine Thyroxine, T3 and T4 Melatonin Serotonin

3 Rule: All hormones interact with target cells by
first binding to specific receptors located either on the plasma membrane or as a cytosolic protein Rule: The receptor for hormones must be linked to a component that is able to respond to the binding of hormone with its receptor Rule: Substances that fool the responder into thinking a hormone has bound are call agonists Rule: Substances that prevent the binding of the natural hormone and do not elicit a response from the receptor are called antagonists

4 1 3 4 5 2 Ca2+ 1 5 2 Nitric oxide 3 4 Insulin IP3 Protein substrates
T-cell Activation Glucagon Insulin 1 3 4 5 2 G G G IP3 G G protein Tyrosine kinase Protein substrates Cyclic AMP Cyclic GMP Ca2+ Diacylgycerol Calmodulin PK-C PK-A PK-G Protein Ser/Thr kinases Protein substrates Protein substrates Multifunctional kinases End result is phosphorylation of one or more proteins Other phospholipases Protein substrates

5 Hypothalamus Anterior pituitary Nervous Releasing hormones
Posterior pituitary Thyrotropin Somatotropin FSH Vasopressin Prolactin LH Oxytocin ACTH Adrenal Cortex Adrenal Medulla Thyroid Pancreas Ovary Testis Cortisol aldosterone Insulin, glucagon, somatostatin Estradiol Testosterone T3 Epinephrine Reproductive organs Muscles liver Liver, muscles Mammary glands Tissues

6 Feedback Loops Rule: Hormones elicit their own shut off mechanism
Hypothalamus Anterior Pituitary Corticotropin releasing factor Adrenal Cortex + -Corticotropin + Cortisol

7 Rule: All peptide hormones are synthesized as
inactive “pre-pro” precursors Rule: A signal peptide must be cleaved off to activate the mature form of the hormone

8 Signal Transduction Action
Definition: The series events and components that take part in transmitting a hormonal signal to a the interior of the cell Membrane or cytosolic Receptor Signal Initiator Action Signal mediator Target molecule

9 Cyclic AMP System Receptor G-protein Adenylate cyclase c-AMP
Stimulate (Gs) and inhibit (Gi) Adenylate cyclase c-AMP Protein kinases

10 G-Proteins A family of membrane proteins that exist in an inactive
(GDP) and an active (GTP) state So-named because they bind GTP, displacing GDP Work with many receptors Both Stimulate and inhibit hormone signals GTP is a time-bomb slowly ticking When GTP is hydrolyzed to GDP, stimulation is stopped

11 Resting Active Inactive Resting GTP AC ATP AC cAMP AC PO4 AC GDP GTP

12 Adenylate cyclase Signaling System Cell response hormone Inhibitor Ri
RS AC GTP GDP GDP 4 ATP GTP AT P Inactive protein ADP Protein kinase 4 cAMP Adenylate cyclase Signaling System Active protein Cell response

13 Tyrosine Kinase Receptors
Ligand N Cross phosphorylation C Tyrosine Kinase Receptors

14 Growth Hormone Receptor
Extracellular Growth hormone Extracellular domain of Growth Hormone Receptor Binding to receptor forces dimerization of receptor subunits for cross phosphorylation =O3PO- -OPO3= Tyrosines Cell membrane (lipid bilayer) Intracellular Growth Hormone Receptor

15 Take Home Most hormones never penetrate cells
All hormones have receptors Internal responses are initiated by the receptor Receptors work with G proteins G proteins stimulate protein kinases Protein kinases comprise a cell signaling cascade G proteins turn off when GTP is hydrolyzed to GDP, canceling the hormone action

16 Take Home (Part 2) Some receptors are protein tyrosine kinases
Kinase activity is initiated by dimerization Kinase autophosphorylate receptors Phosphotyrosines bind to SH-2 domains Activation starts a kinase cascade Phosphorylated proteins enter nucleus DNA transcription turns on specific genes


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