Facilitation of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation after activation of catecholaminergic pathways or central norepinephrine injection.

The functional role of central catecholamines in regulation of ACTH secretion remains controversial. In the present report, the nature of catecholaminergic influences was directly assessed by measurement of hypophysial-portal plasma immunoreactive CRF (irCRF) levels after activation of endogenous aminergic pathways by electrical stimulation or administration of norepinephrine (NE). Electrical stimulation of the ventral noradrenergic ascending bundle, a fiber system primarily carrying catecholaminergic fibers arising from brainstem regions, resulted in a 2.9-fold elevation of portal irCRF levels. Pretreatment with the alpha 1-adrenergic receptor antagonist coryanthine, but not the beta-adrenergic antagonist propranolol, blocked the facilitatory effect of electrical stimulation and reduced prestimulation irCRF levels by 34.7 +/- 4.2% (P less than 0.05). Intracerebroventricular administration of 0.1-5.0 nmol NE resulted in a dose-dependent facilitation of portal plasma irCRF levels which could be blocked by pretreatment with coryanthine. Alternatively, administration of greater than or equal to 5 nmol NE caused a dose-dependent inhibition of irCRF release which could be prevented by pretreatment with propranolol. Finally, irCRF secretion evoked by nitroprusside-induced hypotension was also blocked by pretreatment with coryanthine, but not propranolol. These observations provide strong evidence in favor of a predominantly stimulatory action of NE (and possibly epinephrine) at the hypothalamic level to evoke secretion of CRF and thus to activate the pituitary-adrenal axis.