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Testis |
-Reductase Isoenzymes 1 and 2 in the Rat Testis During Postnatal Development1
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia
The pubertal initiation of spermatogenesis is reliant on androgens, and during this time, 5
-reduced androgens such as dihydrotestosterone (DHT) are the predominant androgens in the testis. Two 5
-reductase (5
R) isoenzymes (5
R1 and 5
R2) have been identified, which catalyze the conversion of testosterone to the more potent androgen DHT. The present study aimed to investigate the developmental pattern of 5
R isoenzymes and their relationship to the production of 5
-reduced androgens in the postnatal rat testis. Both 5
R1 and 5
R2 isoenzyme mRNAs were measured by real-time polymerase chain reaction, isoenzyme activity levels by specific assays, and testicular androgens by radioimmunoassay after high-performance liquid chromatographic separation. Both 5
R1 and 5
R2 mRNAs and activity levels were low in the 10-day-old (prepubertal) testis, peaked between Days 20 and 40 during puberty, and then declined to low levels at 60160 days of age. The developmental pattern of both 5
R isoenzyme activity levels was mirrored by the testicular production of 5
-reduced metabolites. Although 5
R1 was greater than 5
R2 at all ages, it is likely, given the substrate preferences of the two, that both isoenzymes contribute to the pubertal peak of 5
-reduced androgen biosynthesis. The peak in 5
R isoenzymes and 5
-reduced metabolite production coincided with the first wave of spermatogenesis in the rat, suggesting a role for 5
-reduced metabolites in the initiation of spermatogenesis. This was explored by acute administration of a 5
R inhibitor (L685,273) to immature rats. The L685,273 markedly suppressed testicular 5
R activity during puberty by 75%86%. However, a marked increase was observed in testicular testosterone levels (in the absence of changes in LH), and no decrease was observed in the absolute levels of 5
-reduced metabolites. Therefore, whether the formation of DHT in the presence of low testosterone levels in the pubertal testis is required for the initiation of spermatogenesis cannot be tested using 5
R inhibitors. We conclude that both 5
R1 and 5
R2 isoenzymes are involved in the peak of 5
-reduced androgen biosynthesis in the testis during the pubertal initiation of spermatogenesis.
2 Correspondence: Liza O'Donnell, Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton 3168, Australia. FAX: 61 03 9594 6125; liza.odonnell{at}med.monash.edu.au
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