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 vasopressin (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), whereas 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%, whereas 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. We conclude that: 1) CRF originating from neurons within the PVN is the predominant regulator of stress-induced ACTH secretion; 2) catecholamines and AVP are involved in mediating stress-induced ACTH secretion, most probably as CRF-potentiating agents; and 3) pituitary hyperresponsiveness to exogenous CRF results from removal of endogenous CRF.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D002714:Chlorisondamine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D004986:Ether; D008473:Median Eminence / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000503:physiopathology*; D014667:Vasopressins / Q000037:antagonists & inhibitors
D004986:Ether; D014667:Vasopressins; D001127:Arginine Vasopressin; C028888:argipressin, deaminopenicillamine(1)-O-methyl-Tyr(2)-; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D002714:Chlorisondamine; D003345:Corticosterone