Maximal Testosterone Production in Leydig Cells from Inbred Mice Relates to the Activity of 3β-Hydroxysteroid Dehydrogenase-isomerase*

Abstract

Significant differences in maximal testosterone production by Leydig cells from the following strains of inbred mice: C57BL/10J, C57BL/6J, DBA/2J, and C3H/HeJ were observed. To evaluate whether these differences in maximal testosterone production related to the activities of the steroidogenic enzymes of the smooth endoplasmic reticulum of Leydig cells from these strains, the activities of 3.beta.-hydroxysteroid dehydrogenase-isomerase, 17.alpha.-hydroxylase, C17-20 lyase, and 17-ketosteroid reductase were measured in homogenates of purified Leydig cells using 3H-labeled substrates and measuring the amounts of 3H products formed. Maximal and basal testosterone production were determined by incubating aliquots of Leydig cells for 2 h in the presence or absence of 30 pM hCG [human chorionic gonadotropin]. Maximal testosterone production by Leydig cells from C57BL/10J and C57BL/6J mice was significantly greater than that by Leydig cells from DBA/2J and C3H/HeJ mice. No difference in basal testosterone production was observed among the strains. Among the 4 enzymes studied, only 3.beta.-hydroxysteroid dehydrogenase-isomerase activity was significantly correlated with hCG-stimulated testosterone production by Leydig cells from the 4 strains of mice. When equivalent numbers of Leydig cells from each strain were incubated with an equal concentration of [3H]pregnenolone, a similar difference in [3H]testosterone production was observed among the 4 strains, as was seen with hCG-stimulation. Leydig cells from C57BL/10 and C57BL/6J mice left less [3H]pregnenolone unmetabolized and produced higher amounts of [3H]testosterone than Leydig cells from DBA/2J and C3H/HeJ mice. There was a significant negative correlation between the amount of pregnenolone unmetabolized and the amount of testosterone produced. 3.beta.-Hydroxysteroid dehydrogenase-isomerase may be important in determining the differences in hCG-stimulated testosterone production by Leydig cells from the 4 strains of mice.