Maximal testosterone production in Leydig cells from inbred mice relates to the activity of 3 beta-hydroxysteroid dehydrogenase-isomerase.
We previously described 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. 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. 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 four enzymes studied, only 3 beta-hydroxysteroid dehydrogenase-isomerase activity was significantly correlated with hCG-stimulated testosterone production by Leydig cells from the four strains of mice. In addition, 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 four 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. These data suggest that 3 beta-hydroxysteroid dehydrogenase-isomerase may be important in determining the differences in hCG-stimulated testosterone production by Leydig cells from the four strains of mice.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000446:Aldehyde-Lyases / Q000378:metabolism; D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism; D011375:Progesterone Reductase; D013045:Species Specificity; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013251:Steroid Isomerases / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D013739:Testosterone; D011284:Pregnenolone; D015096:3-Hydroxysteroid Dehydrogenases; D011375:Progesterone Reductase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases; D013251:Steroid Isomerases