EFFECT OF PARAVENTRICULAR LESIONS ON CORTICOTROPIN-RELEASING FACTOR (CRF)-LIKE IMMUNOREACTIVITY IN THE STALK-MEDIAN EMINENCE - STUDIES ON THE ADRENOCORTICOTROPIN RESPONSE TO ETHER STRESS AND EXOGENOUS CRF

Corticotropin-releasing factor-like immunoreactivity (CRF) and plasma ACTH were measured in rats bearing bilateral lesions of the paraventricular nucleus (PVN). Four to 6 days after stereotaxic surgery, CRF-like immunoreactivity content of the stalk-median eminence was reduced by 87-90% and the ACTH response to a 3-min ether stress was greatly attenuated (70-85% reduction). In order to differentiate between possible effects of CRF, catecholamines and arginine-vasopression (AVP), the following treatments were used: group I, sham/vehicle; group II, sham/AVP-antagonist; group III, sham/ganglionic blocker chorisondamine; group IV, PVN-lesions/vehicle; group V, PVN-lesion/AVP antagonist; group VI, PVN-lesion/chlorisondamine. Blood was sampled at 0, 5 and 15 min after a 3-min exposure to ether vapor. PVN lesions alone greatly attenuated the ACTH response to ether stress by 70-85% (group IV); basal ACTH levels were not affected. Chlorisondamine alone (group III) was as effective as PVN lesions in reducing the secretion of ACTH due to stress. When PVN-lesioned animals were treated with the ganglionic blocker, the residual ACTH response was completely abolished (group VI). The AVP-antagonist alone reduced the response at +15 min by 45%; the antagonist given to PVN-lesioned animals completely abolished the response at 15 min. Injection of 0.15 nmol ovine CRF into PVN-lesioned rats resulted in a dramatically increased ACTH response (328% at 15 min) in comparison to the response of sham-operated rats. CRF originating from neurons within the PVN is the predominant regulator of stress-induced ACTH secretion; catecholamines and AVP are involved in mediating stress-induced ACTH secretion, most probably as CRF-potentiating agents; and pituitary hyperresponsiveness to exogenous CRF results from removal of endogenous CRF.