1. HP(A)-axis and metabolic control BIM23 VT2016 Maria.Bjorkqvist@med.lu.se

2. Litterature This lecture is based on material from; – Boron and Boulpaep, Medical Physiology – Guyton and Hall, Textbook of Medical Physiology

3. Cell – cell communication Paracrine signaling autocrine signaling endocrine signaling Neurocrine signaling Neurotransmission Cell – cell communication

4. Steroids – Testosterone, estrogen, cortisol etc Amines – Adrenaline, noradrenaline, serotonine, dopamine etc Aminoacids, peptides, proteines – Aminoacids (ex glutamate) – Peptides (2-50 aminoacids) ex insulin, angiotensine II – Proteines (>50 aminoacids) Fatty acid derivatives – Tromboxanes, endocannabinoids, leukotrienes Gases – NO Nucleoside derivatives – adenosindiphosphate Cell – cell communication

5. Receptors

6. Corticosteroids and their receptors

7. Endocrine organs and glands

8. HP axeses

9. Hypothalamus

10. Pituitary gland

11. ADH (Vasopressin) and oxytocin

12. Anterior pitutitary

13. Hormones Hypothalamus Anterior pituitary Target organs GHRH, GHIHGHMultiple TRHTSHThyroid gland (T3, T4) CRHACTHAdrenal gland cortex (Corticosteroids) GnRHLH, FSHGonads (Estrogen, testosterone) PIH (dopamine)prolactinBreast

15. Regulation

16. Hormones Hypothalamus Anterior pituitary Target organs GHRH, GHIHGHMultiple TRHTSHThyroid gland (T3, T4) CRHACTHAdrenal gland cortex (Corticosteroids) GnRHLH, FSHGonads (Estrogen, testosterone) PIH (dopamine)prolactinBreast

17. Short on Growth Hormone Stimulates growth (IGF) Stimulates protein synthesis Ketogenic effect (stimulates fat breakdown) Diabetogenic effect (Inhibits the use of glucose) Hypoglycemia and stress - increased secretion Gigantism and acromegaly

20. T3, T4 effects in short Increase basic metabolic rate Regulates protein, fat and carbohydrate metabolism Protein synthesis Synergy with GH (bone growth) Increase catecholamine sensitivity

21. T3, T4

22. HPA axis

23. Adrenal gland

25. Glucocorticoid effects in short Immune suppressor Decrease bone formation Metabolism of fat, protein and carbohydrates – Carbohydrates Stimulation of gluconeogenesis (  blood glucose) – Protein  protein stores (except for in liver)  protein synthesis  protein catabolism  plasma proteins,  liver proteins,  blood AA – Fat Mobilization of fatty acids  FFA in plasma

26. Lessons from Huntington´s disease

27. (van der Burg et al Lancet Neurology 2009) HYPOTHESISBACKGROUNDONGOING PROJECTS

30. HYPOTHESISBACKGROUNDOUR PROJECTS ACTH Cortisol

31. HYPOTHESISBACKGROUNDOUR PROJECTS GH

32. HYPOTHESISBACKGROUNDOUR PROJECTS Melatonin

33. HYPOTHESISBACKGROUNDOUR PROJECTS Melatonin

34. Stress the system? Dexamethasone suppression test GH suppression test