Question

Discuss how glucocorticoid negative feedback suppresses the hypothalamic pituitary adrenal axis (HPA) for the suppression of the stress axis with a reference to experimental evidence. Your answer should include discussion of the receptor signaling pathways glucocorticoids signal through, the time course of action and the cellular functions which are altered following glucocorticoid receptor activation.

Answer 1

The production of glucocorticoids from the adrenal cortex is minimal in the absence of ACTH. ACTH promotes the conversion of cholesterol to pregnenolone. CRH controls the release of ACTH and therefore of Glucocorticoids. Glucocorticoids operate a negative feedback mechanism on anterior Pituitary and hypothalamus. Diurnal variation occurs in the production of glucocorticoids which are high in concentration in circulation in the morning and low in the evening. Any kind of stress induces the release of glucocorticoids. Glucocorticoids are released during stress periods, especially in long term stress. Stress is a nonspecific response to any factor that can threaten homeostasis mechanism. Dramatic increase of glucocorticoid concentrations, mediated by the central nervous system, occurs in response to all kinds of stressful situations. The paraventricular nucleus of the hypothalamus release two neurohormones-CRF and arginine vasopressin -into hypophysial portal blood. Both of these hormones can cause the stimulation of anterior pituitary to secrete ACTH. the released ACTH can induce glucocorticoid - cortisol synthesis from the adrenal cortex. The activation of the HPA axis by the hypothalamus is modulated by neurotransmitter systems. thus there can be inhibitory effect (GABA), and excitatory effect (norepinephrine) on the intraventricular nucleus. Cortisol contains two types of receptors - mineralocorticoid and glucocorticoid receptor. The cortisol can more easily bind to mineralocorticoid receptors than glucocorticoid receptors. but during the stressful situations, with low affinity, the cortisol can bind to the glucocorticoid receptors, as cortisol rate is high. this activation of glucocorticoid receptors can terminate the stress response. hypothalamus stress excites CRF АСТН. sterioidogenesis cortisol adrenal cortex