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

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(11 beta) were used to determine if the agents would effect differential or parallel suppression of 19- vs 11 beta-hydroxylation by gerbil adrenal mitochondria in vitro. The inhibitors (0.1-60 microM) tested (listed in order of decreasing effectiveness) were imazalil, metyrapone, miconazole and 4-hydroxyandrostenedione. With each inhibitor the degree of suppression of 11 beta-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 1 microM to primary cultures of gerbil adrenal cells brought about nearly equal increases in the secretion of 11 beta- and 19-hydroxylated steroids into the culture media. These results support the hypothesis that the 11 beta-hydroxylase of gerbil adrenal mitochondria has the capacity to carry out 11 beta- and 19-hydroxylations with nearly equal facility.