Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

The release of adrenocorticotropin (ACTH) from the corticotrophs is control led principally by vasopressin and corticotropin-releasing hormone (CRH). O xytocin may augment the release of ACTH under certain conditions, whereas a trial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary glan d to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleu s also project to the cerebral cortex and subcortical regions and to the lo cus ceruleus (LC) in the brain stem. Cortical influences via the limbic sys tem and possibly the LC augment CRH release during emotional stress, wherea s peripheral input by pain and other sensory impulses to the LC causes stim ulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by oc-adrenergic receptors. A muscarin ic cholinergic receptor is interposed between the a-receptors and nitric ox idergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygena se and epoxygenase. Vasopressin release during stress may be similarly medi ated. Vasopressin augments the release of CRH from the hypothalamus and als o augments the action of CRH on the pituitary. CRH exerts a positive ultras hort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraven tricular nucleus to augment the release of CRH.