Mechanism of Hormonal Action

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Mechanism of Hormonal Action 22/02/2019 Dr. Omary Chillo (MD, PhD)

What are the general mechanisms of hormonal action? 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Hormone Signaling Cascade Surface Receptors Cytoplasmic Receptors Nuclear Receptors Biological Action 22/02/2019 Dr. Omary Chillo (MD, PhD)

Down Regulations of Receptors Decreased in the number of receptors Receptors destroyed or deactivated Decreases Responsiveness of the target tissue to the hormone 22/02/2019 Dr. Omary Chillo (MD, PhD)

Up Regulations of Receptors Increase in the number of receptors Receptors activated or manufactured Increases responsiveness of the target tissue to the hormone 22/02/2019 Dr. Omary Chillo (MD, PhD)

Intracellular Signaling Hormone-receptor complex Activated Receptor initiates hormonal effects by:- Changing the membrane potential Activating intracellular enzymes Activating genes 22/02/2019 Dr. Omary Chillo (MD, PhD)

Intracellular Signaling Changing the membrane potential Na+ Hormone-receptor complex Activated Receptor Open or close Na+, K+, Ca2+ Eg. Epinephrine and norepinephrine 22/02/2019 Dr. Omary Chillo (MD, PhD)

Intracellular Signaling Activating Intracellular Enzymes Hormone-receptor complex Enzyme A Activated Kinase Molecule P Second Messenger Eg. Insulin 22/02/2019 Dr. Omary Chillo (MD, PhD)

Intracellular Signaling Activating genes Hormone-receptor complex Genetic Transcription e.g. Thyroxine 22/02/2019 Dr. Omary Chillo (MD, PhD)

Second Messenger Mechanisms Enzyme A Second Messengers cyclic AMP/cyclic GMP Calcium-Calmodulin complex Phospholipase C 22/02/2019 Dr. Omary Chillo (MD, PhD)

Adenyl Cyclase-cAMP Mechanisms Gs Protein Enzyme Adenyl Cyclase Examples:- FSH TRH Angiotensin II Glucagon HCG TSH PTH LH ATP Activated cAMP Protein P ADP ATP 22/02/2019 Dr. Omary Chillo (MD, PhD)

Phospholipase C Mechanisms Examples:- Oxytocin GnRH TRH Vasopression Angiotensin II Gs Protein PIP2 IP3 DAG Ca2+ Cell Response 22/02/2019 Dr. Omary Chillo (MD, PhD)

Activated Receptor Calcium-Calmodulin Mechanisms Ca2+ Hormone-receptor complex Activated Receptor Ca2+ binds to Pr-calmodulin Activation of Protein Kinases Eg. Smooth muscle contraction is brought by activation of myosin kinase 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Properties of the hormone effect 1. Specificity The special feature of the target cells is the presence of receptors which can “attract” and interact with the hormone. 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 2. Signal Transmission The role of the hormones is to transit the regulatory signals from the control (endocrine) system to the target cells (organs or glands). It could enhance or inhibit some function of the target. 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 3. High Biological Efficiency Low plasma concentration (nmol – pmol/L) great regulatory function 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 4. Interaction Between the Hormones (1) Synergistic effects. When two or more hormones work together to produce particular result their effect are said to be synergistic. These effects may be additive or complementary. Additive: Same effect of the hormones on one target organ, for example, epinephrine and norepinephrine on the heart rate Complementary: Work on different stages of a physiological procedure, for example, FSH (initiation) and testosterone (maintenance) on spermatogenesis 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) (2) Permissive effect. A hormone is said to have a permissive effect on the action of a second hormone when it enhances the responsiveness of a target organ to the second hormone or when it increases the activity of the second hormone. Estrogen – Expression of progesterone receptors on uterus – progesterone effect on the uterus. Glucocorticoids – effects of catecholamines on cardiovascular system 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) (3) Antagonist Effects. In some situations the actions of one hormone antagonize the effects of another. Lactation during pregnancy is prevented because the high concentration of estrogen in the blood inhibits the milk secretion and action of prolactin. 22/02/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Thanks 22/02/2019 Dr. Omary Chillo (MD, PhD)