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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^*

T. O. BRUHN, P. M. PLOTSKY and W. W. VALE

Peptide Biology Laboratory, The Salk Institute San Diego, California 92138

Presented in part at the 65th Annual Meeting of The Endocrine Society, San Antonio, TX, 1983. Supported in part by NIH Grant AM-26741, the Salk Institute-Texas Research Foundation, the Deutsche Forschungsgemeinschaft Grant BR-794/1-1 (to T.O.B.), and the Mellon Foundation (to P.M.P.). Research conducted in part by the Clayton Foundation for Research, California division.

Abstract

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), 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. (Endocrinology 114: 57, 1984)

Footnotes

^* Presented in part at the 65th Annual Meeting of The Endocrine Society, San Antonio, TX, 1983. Supported in part by NIH Grant AM-26741, the Salk Institute-Texas Research Foundation, the Deutsche Forschungsgemeinschaft Grant BR-794/1-1 (to T.O.B.), and the Mellon Foundation (to P.M.P.). Research conducted in part by the Clayton Foundation for Research, California division.

Clayton Foundation investigator.

Received May 3, 1983.

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