Increased Substrate Concentration Causes a Shift from Production of 11-Oxygenated Androgens to 17,20-Dihydroxyprogestogens during the in Vitro Metabolism of 17-Hydroxyprogesterone by Goldfish Testes

Abstract

Goldfish testes were incubated with [3H] 17-hydroxyprogesterone in the presence of 0 to 100 μg/ml of unlabeled substrate and metabolites examined by thin-layer and high performance liquid chromatography. Conjugated steroids, predominantly sulfates, accounted for 50% of recovered activity with radiolabeled substrate alone, but percentage yields decreased to very low levels with substrate concentrations of 1 μg/ml and above. The 11-oxygenated androgens, androstenetrione and 11-ketotestosterone, were the major products with 0 to 0.1 μg/ml substrate, but at concentrations of 1 to 100 μg/ml the major products were 17,20αdihydroxy-4-pregnen-3-one (30% of recovered activity) with smaller amounts of the 20β-epimer. 11-Deoxycortisol was a minor product at all substrate concentrations. Production of 11-oxygenated androgens in the medium reached a maximum value of 40 ng/100 mg tissue/3 hr with 2 μg substrate, but progestogen production continued to increase up to the maximum substrate used (30 μg at 200 μg substrate). The results demonstrate a clear switch from production of 11-oxygenated androgens to that of 20-reduced progestogens with increased substrate concentration. This switch shows similarities to that observed for in vivo plasma steroid concentrations during the prespawning period of many male teleosts and it is suggested that this, at least in part, may be due to increased substrate availability resulting from elevated gonadotropin secretion.