Influence of the frequency of ovine corticotropin-releasing factor administration on adrenocorticotropin and corticosterone secretion in the rat.

We have examined the pattern of ACTH secretion in rats receiving two or more injections of synthetic ovine corticotropin-releasing factor (CRF). A first exposure of cannulated intact rats to CRF caused a blunting of the ACTH response when CRF was again injected 0.5-6 h later. Since plasma corticosterone levels stayed elevated for only 2 h after the first injection of CRF, the diminished pituitary responsiveness persisted at a time when plasma corticosterone levels had returned to control values. When cannulated adrenalectomized animals were subjected to a similar treatment, the blunting of the ACTH release due to the second injection of CRF, though present, was of significantly shorter duration. Duplication of the corticosterone levels that follow one CRF injection by exogenous administration of the steroid inhibited the subsequent ACTH response to CRF for a maximum of 2 h. Finally, CRF infused into intact rats for 14 days consistently caused elevation of both ACTH and corticosterone secretion. We conclude that CRF administered in a repeated or continuous manner to intact rats, while causing some pituitary desensitization, still elicits a significant degree of ACTH secretion despite the presence of elevated corticosterone release. This observation as well as the fact that CRF-injected adrenalectomized animals exhibit some blunting of their ACTH responses suggest that steroid feedback, while participating in the diminished ability of CRF to repeatedly stimulate ACTH release, does not represent the sole modulator of pituitary responsiveness.