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-Hydroxysteroid Dehydrogenase Oxidative and Reductive Activities in Rat Leydig Cells during Pubertal Development1
a The Population Council and Rockefeller University, New York, New York 10021
The enzyme 3
-hydroxysteroid dehydrogenase (3-HSD) has an important role in androgen metabolism, catalyzing the interconversion of dihydrotestosterone (DHT) and 5-androstane-3,17ß-diol (3-DIOL). The net direction of this interconversion will affect the amount of biologically active ligand available for androgen receptor binding. We hypothesize that in Leydig cells, differential expression of 3-HSD enzymes favoring one of the two directions is a mechanism by which DHT levels are controlled. In order to characterize 3-HSD in rat Leydig cells, the following properties were analyzed: rates of oxidation (3-DIOL to DHT) and reduction (DHT to 3-DIOL) and preference for the cofactors NADP(H) and NAD(H) (i.e., the oxidized and reduced forms of both pyridine nucleotides) in Leydig cells isolated on Days 21, 35, and 90 postpartum. Levels of 3-HSD protein were measured by immunoblotting using an antibody directed against the liver type of the enzyme. Levels of 3-HSD protein and rates of reduction were highest on Day 21 and lowest on Day 90. The opposite was true for the rate of 3-HSD oxidation, which was barely detectable on Day 21 and highest on Day 90 (59.08 ± 6.35 pmol/min per 106 cells, mean ± SE). Therefore, the level of 3-HSD protein detectable by liver enzyme was consistent with reduction but not with oxidation. There was a clear partitioning of NADP(H)-dependent activity into the cytosolic fraction of Leydig cells, whereas on Days 35 and 90, Leydig cells also contained a microsomal NAD(H)-activated 3-HSD. We conclude that 1) the cytosolic 3-HSD in Leydig cells on Day 21 behaves as a unidirectional NADPH-dependent reductase; 2) by Day 35, a microsomal NAD(H)-dependent enzyme activity is present and may account for predominance of 3-HSD oxidation over reduction and the resultant high capacity of Leydig cells on Day 90 to synthesize DHT from 3-DIOL.
2 Correspondence: Matthew P. Hardy, The Population Council, 1230 York Avenue, New York, NY 10021. FAX: 212 327 7678; m-hardy{at}popcbr.rockefeller.edu
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