Biosynthesis of Sexual Steroids by Hyperplastic Adrenal Glands of Castrated Female C₃H/Ep Mice

Abstract

Adrenal cortical tumors develop several months after the removal of the gonads in guinea pigs, several strains of mice, hamsters and rats. These tumors secrete hormones with estrogenic or androgenic potency or with both, depending on the strain. Incubation studies performed with the adrenal glands having nodular hyperplasia from castrated female C3H/Ep mice are described in this report. Progesterone-4-14C, pregnenolone-4-14C and dehydroepiandrosterone- 4-14C were used as substrates. Testosterone, androstenedione, Δ5-androstenediol and adrenosterone were isolated and their radiochemical purity was tentatively established. Estrone, 17β- estradiol, 16-oxoestrone, 17-epiestriol and 11β- hydroxyandrostenedione were also isolated and separated by paper chromatography but their radiochemical purity was not demonstrated. Only the abnormal adrenal glands synthesized testosterone, 177β-estradiol, estrone and 2 neutral unidentified steroids after incubation withprogesterone- 4-14C. The production of 16-oxoestrone and 17-epiestriol was not significantly different in both groups of animals. Production of testosterone from pregnenolone was greater in the hyperplastic adrenal glands than in the normal ones. The production of androstenedione from dehydroepiandrosterone was greater in the abnormal adrenals than in the normal ones, while in the production of 11β-hydroxy androstenedione an opposite ratio was obtained. The apparent discrepancies between the biological observations and biochemical studies are discussed.(Endocrinology79: 681, 1966)