Effect of in Vivo Treatment with Adrenocorticotropin and Hypophysectomy on Adrenal Adenosine 3′,5′-Monophosphate and Corticosterone Responsiveness to Adrenocorticotropin Stimulation in Vitro*

This study examined the effect of in vivo treatment with ACTH for 5 days and hypophysectomy (7–10 days) on adrenal cAMP and corticosterone responsiveness to ACTH in vitro. Basal cAMP in the saline-treated rats was similar to that in the ACTH-treated and hypophysectomized animals. ACTH stimulation of cAMP formation in vitro in both the ACTH-treated and hypophysectomized rats was significantly increased compared to that in the saline-treated controls. Basal corticosterone release was significantly increased in the ACTHtreated animals and decreased in the hypophysectomized rats. The ACTH stimulation of corticosterone release was also significantly augmented in the ACTH-treated rats compared to that in the saline-treated rats, while the value was significantly decreased in the hypophysectomized animals. When adrenal quarters from control rats were initially exposed to ACTH in vitro for 1 h and then incubated for 1 h in buffer alone, the subsequent addition of the hormone in th third incubation caused a diminished cAMP formation compared to tissue which had not been previously incubated with ACTH in the first incubation. The decreased responsiveness was still present if the second incubation was prolonged for 24 h after the initial exposure to ACTH. While the increased responsiveness of cAMP generation in the adrenals from the hypophysectomized rats might reflect increased ACTH receptors as a consequence of deficient endogenous ACTH, such receptor regulation would not account for the increased responsivity of the adrenal from the ACTH-treated rats. The results also emphasize the disparity between previous in vivo and in vitro exposures to ACTH on the subsequent response to that hormone.