Facilitation of Immunoreactive Corticotropin-Releasing Factor Secretion into the Hypophysial-Portal Circulation after Activation of Catecholaminergic Pathways or Central Norepinephrine Injection*

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Abstract
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 norepineprhine (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 < 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.

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