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

Goldfish testes were incubated with [H-3]17-hydroxyprogesterone in the presence of 0 to 100 mu g/l of unlabeled substrate and metabolites ex amined by thin-layer and high performance liquid chromatography. Conju gated steroids, predominantly sulfates, accounted for 50%, of recovere d activity with radiolabeled substrate alone, but percentage yields de creased to very low levels with substrate concentrations of 1 mu g/ml and above. The 11-oxygenated androgens, androstenetrione and 11-ketote stosterone, were the major products with 0 to 0.1 mu g/ml substrate, b ut at concentrations of 1 to 100 mu g/ml the major products were 17,20 alpha-dihydroxy-4-pregnen-3-one (30% of recovered activity) with smal ler amounts of the 20 beta-epimer. 11-Deoxycortisol was a minor produc t at all substrate concentrations. Production of 11-oxygenated androge ns in the medium reached a maximum value of 40 ng/100 mg tissue/3 hr w ith 2 mu g substrate, but progestogen production continued to increase up to the maximum substrate used (30 mu g at 200 mu g substrate). The results demonstrate a clear switch from production of 11-oxygenated a ndrogens to that of 20-reduced progestogens with increased substrate c oncentration. This switch shows similarities to that observed for in v ivo plasma steroid concentrations during the prespawning period of man y male teleosts and it is suggested that this, at least in part, may b e due to increased substrate availability resulting from elevated gona dotropin secretion. (C) 1994 Academic Press, Inc.