A series of in vitro experiments using 414C-pregnenolone and 414C-progesterone as precursors were performed to determine the effects of prolonged adrenocorticotrophic hormone (ACTH) administration on adrenal steroid biogenesis in rabbits. The adrenal steroids were isolated by paper chromatography and quantitated by the double isotope derivative assay method. In the control group, there was no distinction between the roles of pregnenolone and progesterone as precursors of adrenal steroids. Following the administration of 25 U of porcine ACTH for 21 days, however, 17α-hydroxylated steroids became quantitatively important. Prolonged exogenous ACTH treatment enhanced the specific activities of the 17α-hydroxycorticosteroids from both precursors, but the specific activities were enhanced more from pregnenolone than from progesterone. Under experimental conditions more than twice as much pregnenolone was metabolized via 17α-hydroxypregnenolone bypassing the progesterone step than under control conditions. Prolonged ACTH administration appeared to stimulate the 17α-hydroxylase enzyme system.
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