LOCALIZATION AND REGULATION OF 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-3 MESSENGER-RNA DURING DEVELOPMENT IN THE MOUSE TESTIS

The final step in the biosynthesis of testosterone is the reduction of androstenedione to testosterone catalysed by the enzyme 17 beta-hydro xysteroid dehydrogenase (17 beta HSD). Five isoforms of the enzyme hav e been identified in the mouse and the type 3 isoform has been shown t o be the predominant reductive form present in the adult human and mou se testis. In this study the regulation of 17 beta HSD type 3 isoform mRNA levels and the cellular localisation of the enzyme mRNA have been studied in the mouse testis. To examine regulation of 17 beta HSD typ e 3 mRNA expression in the testis, mRNA levels were measured during de velopment in normal mice and in mice lacking circulating gonadotrophin s (hpg) or functional androgen receptors (Tfm). In these mutants testi cular descent does not occur at the normal time (25 days) and control animals were, therefore, rendered cryptorchid at 19 days. In neonatal mice, it has been shown a peak of type 3 expression occurs around day 5 and this was found to be normal in all groups in the current study. In normal animals there was a marked increase in type 3 isoform expres sion between 25 and 30 days and this continued into adulthood. In cryp torchid animals the increase in type 3 mRNA levels after 25 days was l ess marked than in untreated controls and by 90 days was about 15% of normal animals. In Tfm mice, levels of 17 beta HSD type 3 mRNA failed to show any increase around puberty (25 days) and in adult Tfm mice, l evels were less than 1% of cryptorchid controls. In hpg mice, levels o f type 3 mRNA increased slowly after puberty and were about 30% of cry ptorchid controls by 90 days. Studies using in situ hybridisation show ed that the type 3 isoform was expressed only in the interstitial tiss ue of the adult normal mouse testis. No specific hybridisation could b e determined in adult hpg or Tfm testes. Results show that 17 beta HSD type 3 is an interstitial enzyme in the testis and is, probably, loca lised in the Leydig cells. During neonatal development expression of 1 7 beta HSD type 3 is independent of gonadotrophin action while the inc rease in type 3 expression at puberty is primarily dependent upon andr ogen action although testicular descent and gonadotrophins are also re quired. (C) 1997 Elsevier Science Ltd.