1. Adrenal Cortex Hormones Corticosteroids Immunity & Inflammation reduced Tissue Phosphorylase Glycogen Glucose Mineralocorticoids Kidneys Retain Na+ Retain H2ORetain pressure ‘Health risk?”

2. 1.Steroid passively diffuses across cell membrane. 2.The steroid is bound by receptor in cytoplasm. 3.There is a change in the conformation of the steroid receptor. 4.The steroid-receptor complex moves into the cell nucleus. 5.The steroid-receptor complex associates with the chromatin (DNA) and initiates genetic transcription. (The receptor is a transcription factor.) 6.Synthesis of messenger RNA (mRNA) changes. 7.The mRNA moves into the cytoplasm where it is translated into protein. 8.The protein(s) are processed into their final form. Mechanism of steroid and thyroid hormone action

3. Steroids: schema to depict diversity of mechanisms for their immediate, intermediate and long-term actions in neurons a: Levels of regulation b: Effects on membrane properties

4. Negative Feedback Most biological systems operate with negative feedback protects against overstimulation In the HPA axis, negative feedback via ACTH and cortisol serves to limit excitability of CRF neurons and reduce the impact of their stimulation by a stressor

5. Negative feedback: an important mechanism to regulate release and maintain homeostasis in the HPA axis As levels of both ACTH and cortisol increase, they feed back negatively via receptors on anterior pituitary corticotrophs and hypothalamic CRF secreting neurons, respectively.

6. Figure 18.5 Hypothalamic Control over the Endocrine System: the rapid “neural” pathway from PVN parvocellular neurons that project to spinal sympathetic preganglionic neurons whose axons directly innervate adrenal medulla

7. What is special about adrenomedullary sympathetic preganglionic neurons? Most preganglionic neurons that form the spinal outflow for the peripheral sympathetic nervous system send their axons to a ganglia where they synapse with the postganglionic neurons EXCEPT the preganglionic neurons that innervate the adrenal medulla where the pathway is direct to the chromaffin cells, which serve as analogues of the postganglionic neurons This cholinergic innervation is via the splanchnic nerve, and triggers the chromaffin cells to release adrenaline and noradrenaline in proportion to the firing frequency of adrenomedullary preganglionic neurons

8. 450ms 40mV 10mV Cell 1 Cell 2 Cell 1Cell 2

9. Adrenal Medulla: histology

10. Noradrenaline and adrenaline synthesis

11. Adrenal Medulla Hormones Adrenaline & Noradrenaline Speed heart beat Constrict vessels Increase breathing Dilate airways Perspire Tissue Phosphorylase Lipase Glycogen Fat Glucose Fatty Acids (Also ‘targets’ of Sympathetic nerves)

12. Summary:HPA axis and hypothalamic-spinal-adrenal axis HYPO “Stressors” (from PNS or Cortex) PIT Kidney ADRENAL GLAND ACTH Sympathetic Cortex Medulla Mineralocorticoids Corticosteroids Adrenaline Noradrenaline

13. Features of the mammalian adrenal gland Encased in a connective tissue capsule attached to the upper edge of the kidneys Gland is partitioned into cortex and medulla Organ is richly vascularized, distinct capillary beds supply medulla and cortex Medulla: –arteries penetrate the cortex without branching –fairly homogeneous, composed of chromaffin cells –unique directly innervation by sympathetic preganglioninc neurons –chromaffin cells are analogous to sympathetic postganglion neurons –produce adrenaline (75-80%) and noradrenaline (25-30%) Cortex: –its own blood supply, three distinct functional zones –Zona glomerulosa, outermost, thin, produces mineralocorticoids (aldosterone) –Zona fasiculatat, middle, thickest, produces glucocorticoids (cortisol) –Zona reticulosa, innermost, thin, produces sex steroid (androgens)

14. What the heck is “Stress”?

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16. Types of stress

17. Stressors in Your Life?

18. Some definitions of stress

20. Triad of systems mediate response to stress

21. Stress = any condition that threatens homeostasis GAS (General Adaptation Syndrome) is our bodies response to stress-causing factors Three phases to GAS –Alarm phase (immediate, fight or flight, directed by the sympathetic nervous system) –Resistance phase (dominated by glucocorticoids) –Exhaustion phase (breakdown of homeostatic regulation and failure of one or more organ systems) Hormones and stress

22. GAS: immediate response

23. Schematic “overview” of the neural components of a stress “response”

25. Alarm → Resistance phase: bringing the HPA axis and glucocorticoids into play