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Summary

Summary. Hypothalamic-pituitary-adrenal axis Aldosterone Cortisol Adrenal Androgens Medical problems. Adrenal Cortex Physiology. A ldosterone ( mineralocorticoid )  the cortisol ( glucocorticoids ) and androgenic hormones. . Angiotensin II. ACTH. Adrenal Morphology.

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Summary

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  1. Summary • Hypothalamic-pituitary-adrenal axis • Aldosterone • Cortisol • Adrenal Androgens • Medical problems

  2. Adrenal Cortex Physiology • Aldosterone(mineralocorticoid)  • the cortisol (glucocorticoids) and • androgenic hormones. Angiotensin II ACTH

  3. Adrenal Morphology Zonaglomerulosa Aldosterone Zonafasciculata Glucocorticoids Zonareticularis Androgens

  4. Hypothalamus CRH Anterior Pituitary ACTH Adrenal Cortex (Zona Fasciculata Zona Reticularis) Cortisol / Androgens

  5. Hypothalamus CRH Anterior Pituitary ACTH (minor) Angiotensin II K+ Adrenal Cortex (Zona Glomerulosa) Aldosterone

  6. Corticotropin Releasing Hormone • Peptide hormone • Released both diurnally and pulsatile • Released by hypothalamus and placenta • Travels bound to CRH-binding protein • Important wrt active concentration • Stimulates ACTH release

  7. Corticotroph CRH Vesicles containing ACTH cAMP Via PKA Release of ACTH via exocytosis Ca2+

  8. ACTH • 39 amino acids • Synthesized in corticotrophs of AP • Half-life of ~ 10 minutes pro-opiomelanocorticotrophin (POMC) Beta- lipotropin(β –LPH) a-melanocyte-stimulating hormone (a-MSH)

  9. Schematic overview of the structures of steroid-secreting cells and the intracellular pathway of steroid synthesis : ACTH

  10. At the adrenal gland • StAR- Steroidal Acute Regulatory protein ACTH LDL Cholesterol LDL StAR Lysosomes Mitochondria

  11. Some of the short and long-term actions of ACTH Short-term Conversion of cholesterol into pregnenolone ACTH Transcription of synthesis enzymes Number of LDL receptors Long-term

  12. adrenarche cholesterol side-chain cleavage enzyme (RLE*) *RLE-Rate Limiting Enzyme.

  13. Aldosterone Synthesis

  14. Hypothalamus CRH Anterior Pituitary ACTH (minor) Angiotensin II K+ Adrenal Cortex (Zona Glomerulosa) Aldosterone

  15. At the adrenal gland A-II K+ Depolarization DAG IP3 Ca2+ Activation of aldosterone synthesis Activation of PKC

  16. At the target tissues • To maintain blood volume • K+ homeostasis • Retain Na+ levels in the body • Via kidneys, saliva, sweat and GIT Aldosterone Enzymes Transport proteins Modulation of gene expression

  17. Distal tubule and collecting duct Plus Aldosterone Na+ K+ Na+ K+ Interstitial Fluid Principal Cell Lumen

  18. Hypothalamus CRH • Blood volume • GFR renin release Anterior Pituitary K+ secretion ACTH (minor) Angiotensin II K+ Adrenal Cortex (Zona Glomerulosa) Aldosterone

  19. Hypersecretion • Tumor in the Zonaglomerulosaor increased renin secretion • Effects:- • Increased extracellular fluid volume • Hypertension • Hypokalemia • Muscle weakness, arrhythmias

  20. Hyposecretion • Hyperkalemia • Hyponatremia • Decreased extracellular fluid volume • Shock

  21. Hypothalamus CRH Anterior Pituitary ACTH Adrenal Cortex (Zona Fasciculata Zona Reticularis) Cortisol

  22. At the adrenal gland ACTH cAMP Phosphorylation of proteins Protein Kinase A

  23. At the target tissues Cortisol Many effects Modulation of gene expression

  24. Action of Insulin Inhibited by Cortisol?? glucose Energy General cell Fatty acids glycerol glucose Amino Acids glycogen Liver Protein breakdown lipolysis Plasma proteins Muscle Adipose Cells

  25. Other effects • Modulates behaviour and mood • Maturation of the fetus • Role in parturition????? • Modifies and controls both inflammatory and immune responses • Important in stress response (later)

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