Gerbil adrenal 11β- and 19-hydroxylating activities respond similarly to inhibitory or stimulatory agents: Two activities of a single enzyme

Abstract

A high level of steroid 19-hydroxylation is exhibited by adrenal mitochondria of the gerbil, Meriones, unguiculatus, that accounts for the ability of that species to produce nearly equal amounts of corticosterone and 19-hydroxycorticosterone ( Proc. Soc. exp. Biol. Med. 165 (1980) 69–74). Inhibitors of steroidogenesis and a polyclonal antibody against bovine cytochrome P-450 11β were used to determine if the agents would effect differential or parallel suppression of 19- vs 11β-hydroxylation by gerbil adrenal mitochondria in vitro. The inhibitors (0.1–60 μM) tested (listed in order of decreasing effectiveness) were imazalil, metyrapone, miconazole and 4-hydroxyandrostenedione. With each inhibitor the degree of suppression of 11β-hydroxylation was accompanied by a parallel decline in 19-hydroxylation. The addition of the polyclonal antibody preparation also produced equivalent declines in the rates of the two hydroxylation reactions. The addition of ACTH 1μM to primary cultures of gerbil adrenal cells brought about nearly equal increases in the secretion of 11β- and 19-hydroxylated steroids into the culture media. These results support the hypothesis that the 11β-hydroxylase of gerbil adrenal mitochondria has the capacity to carry out 11β- and 19-hydroxylations with nearly equal facility.