Studies on corticotropin-induced desensitization of normal rat adrenocortical cells

Sheela Rani, C. S. ; Keri, G. ; Ramachandran, J. (1983) Studies on corticotropin-induced desensitization of normal rat adrenocortical cells Endocrinology, 112 (1). pp. 315-320. ISSN 0013-7227

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Official URL: http://endo.endojournals.org/cgi/content/abstract/...

Related URL: http://dx.doi.org/10.1210/endo-112-1-315

Abstract

The effects of prior exposure of normal rat adrenocortical cells to ACTH on the responsiveness of the cells to subsequent stimulation with the hormone have been studied. ACTH induces a time- and concentration-dependent refractoriness of both cAMP formation and steroidogenesis. Desensitization of either response was observed only upon activation of the response. Thus, both ACTH and 8-Br-cAMP caused desensitization of the steroidogenic response. The ACTH-induced desensitization of steroidogenesis, however, was completely prevented by blocking the steroidogenic action of ACTH with aminoglutethimide during exposure of cells to the hormone. Aminoglutethimide had no effect on ACTH-induced desensitization of the cAMP response. Studies with analogs of the hormone also confirmed that induction of desensitization of the steroidogenic response is independent of the desensitization of the cAMP response. Binding studies showed that the insignificant decrease in ACTH receptors could not account for the large changes in the responsiveness induced by prior exposure of cells to ACTH. Desensitization of the steroidogenic response appears to result from a defect in the rate-limiting first step of the steroidogenic pathway, namely conversion of cholesterol to pregnenolone.

Item Type:Article
Source:Copyright of this article belongs to Endocrine Society.
ID Code:40892
Deposited On:25 May 2011 09:33
Last Modified:25 May 2011 09:33

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