Mechanism of Hormone Action
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This presentation deals with the different mechanisms whereby hormones act to target cells/tissues,
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Mechanism of Hormone Action
- 2. Mechanism of Hormone Action
- 3. Mechanism of Hormone Action
- 4. Hormone receptors For protein & peptide hormones – receptor is in plasma membrane For steroid hormones – receptor is in nucleus For prostaglandin hormones – receptor is in plasma membrane
- 5. MOA OF PROTEIN HORMONES
- 7. Steps in protein hormone action 1. Hormone-receptor binding 2. G-Protein activation 3. Adenylate cyclase activation 4. Protein kinase activation 5. Synthesis of new products
- 8. Mechanism of Hormone Action Receptor Protein Kinase A (PKA) Nucleus DNA Protein Synthesis (Enzymes) Plasma Membrane Protein Hormones (cAMP second messenger) C R R-ER Protein Synthesis Mitochondria S-ER Steroid Synthesis LH G Adenylate Cyclase
- 9. Mechanism of Hormone Action Receptor Protein Kinase A (PKA) Nucleus DNA Protein Synthesis (Enzymes) Plasma Membrane Protein Hormones (cAMP second messenger) G Adenylate Cyclase C R cAMP LH ATP cAMP C R R-ER Protein Synthesis Mitochondria S-ER Steroid Synthesis
- 10. C R cAMP Mechanism of Hormone Action Receptor Protein Kinase A (PKA) Nucleus DNA Histones Protein Synthesis (Enzymes) Plasma Membrane Protein Hormones (cAMP second messenger) G Adenylate Cyclase LH ATP cAMP (+ PO4) R-ER Protein Synthesis Mitochondria S-ER Steroid Synthesis mRNA
- 11. Mechanism of Hormone Action Receptor Protein Kinase A (PKA) Nucleus DNA Histones Protein Synthesis (Enzymes) mRNA Plasma Membrane Protein Hormones (cAMP second messenger) Cholesterol G Adenylate Cyclase C R cAMP LH ATP cAMP (+ PO4) R-ER Protein Synthesis Mitochondria CholesterolPregnenolone S-ER Steroid Synthesis Testosterone
- 12. Mechanism of Hormone Action Receptor Protein Kinase A (PKA) Nucleus DNA Histones Protein Synthesis (Enzymes) mRNA Plasma Membrane Protein Hormones (cAMP second messenger) Cholesterol G Adenylate Cyclase C R cAMP LH ATP cAMP (+ PO4) R-ER Protein Synthesis Mitochondria CholesterolPregnenolone S-ER Steroid Synthesis Testosterone
- 13. cAMP Second Messenger Hormones • Anterior Pituitary Hormones LH, FSH, Prolactin STH, ACTH, TSH • Placental Hormones HCG, eCG
- 14. Protein Hormones (Ca2+ Second Messenger) PLC Endoplasmic Reticulum Ca2+ Protein Kinase C Plasma Membrane GnRH Receptor G-protein R Plasma Membrane Secretory Granules PIP2
- 15. Protein Hormones (Ca2+ Second Messenger) PLC PIP2 Endoplasmic Reticulum Ca2+ Plasma Membrane GnRH Receptor G-protein R Plasma Membrane Secretory Granules PIP2 Protein Kinase C
- 16. Protein Hormones (Ca2+ Second Messenger) PLC PIP2 Endoplasmic Reticulum Ca2+ Protein Kinase C Plasma Membrane GnRH Receptor G-protein DAG IP3 R Ca2+ Plasma Membrane Secretory Granules R PIP2
- 17. Protein Hormones (Ca2+ Second Messenger) PLC PIP2 Endoplasmic Reticulum Ca2+ Protein Kinase C Plasma Membrane GnRH Receptor G-protein DAG IP3 R Ca2+ Plasma Membrane Ca2+ Secretory Granules R PIP2
- 18. Protein Hormones (Ca2+ Second Messenger) PLC PIP2 Endoplasmic Reticulum Ca2+ Protein Kinase C Plasma Membrane GnRH Receptor G-protein DAG IP3 R Ca2+ Plasma Membrane Ca2+ LH Fusion Secretory Granules R PIP2
- 19. Calcium Second Messenger Hormones GnRH Triggers release of LH in anterior pituitary Oxytocin Triggers contractions of smooth muscle PGF2α Triggers apoptosis of cell Inhibition of progesterone synthesis
- 20. Steroid Hormone Action (Slow) Cytoplasm Cell Membrane DNA Receptor Nucleus Steroid (estrogen) Diffusion? mRNAR-ER Protein synthesis New Protein Change in Cell Physiology
- 21. Steroid Hormone Mechanism Estradiol Progesterone Testosterone, Dihydrotestosterone Cortisol
- 22. Steroid Hormone (Fast) Receptor Protein Kinase A (PKA) Nucleus DNA Histones Protein Synthesis (Enzymes) mRNA Plasma Membrane (cAMP second messenger) G Adenylate Cyclase C R cAMP Estradiol ATP cAMP (+ PO4) R-ER Protein Synthesis Ca2+ Ca2+ Smooth Muscle Contraction (Uterine Myometrial Cell)
- 23. Steroid Hormone (Fast) Not the classical mechanism of action of a steroid hormone Requires plasma membrane receptor Operates via protein kinase activation Estradiol – smooth muscle of uterus
- 24. Positive & Negative Feedback Major “controllers” of reproductive hormones Positive feedback – stimulation of GnRH Negative feedback – suppression of GnRH
- 25. Progesterone Causes strong negative feedback Strongly inhibits GnRH neurons – when progesterone is high, there is only a basal secretion of GnRH Females under progesterone (midcycle or pregnant) do not cycle for a period of time that progesterone is high
- 26. Estradiol When estradiol reaches a threshold level, the surge center releases large quantities of GnRH Causes release large quantities of LH that stimulate ovulation
- 27. Endocrine Feedback Loops Negative gonadal steriods Testosterone, Progesterone, Estradiol Protein hormones inhibin Positive Gonadal steroids estradiol
Notas do Editor
- Hormone action requires the presence of receptors.
- Hormones (green spheres) are produced by the cells of the endocrine gland and are released into the blood. The blood delivers the hormones to the target tissue.
- TARGET TISSUES contain receptors (orange) that specifically bind the hormone. NONTARGET TISSUES also have receptors but for other hormones. The specific hormone here will not bind to these receptors. HORMONES WILL ONLY BIND TO THEIR TARGET TISSUES – CONTAIN SPECIFIC RECEPTORS FOR THAT HORMONE. NON-TARGET TISSUE WILL NOT RESPOND. Once the hormone binds to its specific receptor in the target tissue, the target tissue performs its function.
- Different hormones act on different types of receptors.
- HYPOTHETICAL MODEL OF A RECEPTOR FOR A PROTEIN HORMONE (LH) Receptors for protein hormones are integral part of the plasma membrane. They have 3 distinct regions – these regions are referred as the receptor domains.
- The receptor for protein hormone (LH) are present in the plasma membrane
- HORMONE-RECEPTOR BINDING (1) The hormone (LH) binds to a specific receptor in the plasma membrane. ACITVATION OF THE G-PROTEIN (2) The formation of a hormone-receptor complex activates G-PROTEIN (a membrane-bound enzyme). G-PROTEIN is transformed and this activates another membrane-bound enzyme – ADENYLATE CYCLASE. ADENYLATE CYCLASE converts ATP to cAMP.
- CYCLIC AMP activates PROTEIN KINASES (cytoplasm). The regulatory subunit binds cAMP and this causes activation of the catalytic subunit that initiates conversion of existing substrates to new products.
- SYNTHESIS OF NEW PRODUCTS (4)– products made by the cell are secreted In this figure, since the final product is testosterone, we can assume that the target tissue is the LEYDIG CELLS OF THE TESTIS. LH can also bind with the target tissue OVARY (FOLLICLE CELLS) to produce estradiol.
- The target enzyme is phospholipase C (PLC).
- PLC splits phosphatidyl 4,5, bisphosphate (PIP2) into diacylglycerol (DAG) and Inositol 1,4,5 trisphosphate (IP3). IP3 acts by binding to IP3 receptors on the endoplasmic reticulum (ER), and releasing the Ca2+ stored within. IP3 receptors are Ca2+ channels, activated by IP3 binding.
- STEPS OF STEROID HORMONE SYNTHESIS Steroid transport Movement through the cell membrane and cytoplasm Binding of steroid to nuclear receptor – specific nuclear receptor (if the cell is a target cell) MRNA synthesis and protein sysnthesis – MRNA leaves the nucleus and attaches to ribosomes where it directs synthesis of specific proteins
- *Example of a hormone that exhibits a strong negative feedback
- *Example of a hormone that exhibits a strong positive feedback
- FEMALE FEEDBACK DIAGRAM
- MALE FEEDBACK DIAGRAM