HP(A)-axis and metabolic control BIM23 VT2016

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

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

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

Receptors

Corticosteroids and their receptors

Endocrine organs and glands

HP axeses

Hypothalamus

Pituitary gland

ADH (Vasopressin) and oxytocin

Anterior pitutitary

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

Regulation

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

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

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

T3, T4

HPA axis

Adrenal gland

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

Lessons from Huntington´s disease

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

HYPOTHESISBACKGROUNDOUR PROJECTS ACTH Cortisol

HYPOTHESISBACKGROUNDOUR PROJECTS GH

HYPOTHESISBACKGROUNDOUR PROJECTS Melatonin

HYPOTHESISBACKGROUNDOUR PROJECTS Melatonin

Stress the system? Dexamethasone suppression test GH suppression test