1. HPA and Stress MCB 135K Lecture 39

2. kidney adrenal Anterior pituitary Posterior pituitary hypothalamus glucocorticoids

3. Figure 10.2

4. Figure 10.3 Diagram of a section of the adrenals illustrating the various zones and hormones

5. Reminder CRH: corticotropic releasing hormone ACTH: adrenocorticotropic hormone Figure 10.6

7. Actions Of Glucocorticoids Actions of Adrenaline/Noradrenaline Target cellular

8. Figure 10.5 Schematic diagram of corticosteroid action in target cell

9. Gene expression & new protein synthesis Relatively long latency of onset Medium & long term cell program Organization of cell networks for complex functions Activation/repression of pre- existing cell proteins Rapid onset of action Rapid adaptation to changes in the milieu Dynamic modifications of long term cell programs

10. Cortisol, norepinephrine, and epinephrine STRESS

11. Stress: In biology, any change (stressor) in the environment that may tend to alter an existing equilibrium and trigger counteracting responses at molecular, cellular, and systemic levels to preserve/reestablish such an equilibrium and insure adaptation. Claude Bernard, (1813-1878, Prof. of Physiology at the Collège de France, Paris), suggests that the equilibrium or steady state of the “milieu intérieur” is to remain constant to allow for optimal function and survival.

12. Exposure to stress generates: Specific responses: varying with the stimulus and generating different responses with each stimulus Non-Specific responses:always the same, regardless of the stimulus and mediated through stimulation of neural, endocrine & immune axes

13. Some Characteristics of Stress Stress induces defense mechanisms for maintenance of homeostasis in response to environmental challenges

14. Types of Stress Examples of Physical/Chemical Stress –High/low extreme temperatures –Physical injury –Hemorrhage –Hypoglycemia, etc. Examples of Psychological/Emotional Stress –Fear –Cognition of danger –Memories –Sorrow or joy –Hate or love, etc. Sapolsky, R.M., Why Zebras Don’t Get Ulcers: An Updated Guide to Stress, Stress Related Diseases, and Coping, W.H. Freeman and Co., New York, 1998

15. Shift in HPA secretory priorities during stress

16. Table 10.7

17. Pathophysiologic Responses During and After Stress During Stress Energy storage ceases because: Sympathetic activity Parasympathetic activity Insulin secretion Access to energy storage is facilitated & energy storage steps are reversed: glucocorticoid secretion Epinephrine/norepinephrine secretion Glucagon secretion

18. After Stress If physiologic responses are insufficient and adaptation is incomplete, symptoms of poor health are registered (e.g. loss of energy when freeing energy from storage and returning to storage) Examples of consequences: Muscle wasting, Diabetes (Type 2), ulcers, colitis, diarrhea Inhibition of growth (in childhood), Osteoporosis (in old age) LHRH, testosterone

19. Figure 10.10 Some physiologic and pathologic responses to stress in selected organs

20. Elevated Physiologic Indices (at risk) Systolic blood pressure: ≥148 mmHg Diastolic blood pressure: ≥ 83 mmHg Waist-hip ratio: ≥ 0.94 Total cholesterol-High Density Lipoprotein ration: ≥ 5.9 Total glycosylated hemoglobin level: ≥ 7.1% Urinary cortisol level: ≥ 25.7mg/g creatinine Urinary epinephrine level: ≥ 5 mg/g creatinine Urinary norepinephrine level: ≥ 48mg/g creatinine Lowered Physiologic Indices (at risk) HDL cholesterol level: ≤ 1.45 mmol/L DHEA (Dehydroepiandrosterone) level: ≤ 2.5 micro mol/L Risk Factors (Allostatic Load) Endangering Health & Shortening Life Span

21. Janus is the Roman God of gates and doors, of beginnings and endings and, hence, is represented by a double faced head; generally placed on the gates of the city, the menacing face looking towards the outside of the city ready to defend it against any attackers, the benevolent face turned towards the city is a protector and promoter of prosperity and good health.

22. Figure 10.11 Progressive stages of homeostasis from adjustment (health) to failure (death)