Exp Clin Endocrinol Diabetes 2005; 113 - 152
DOI: 10.1055/s-2005-863011

Key-enzymes of human sexual differentiation show tissue specific transcription profiles

U Hoppe 1, PM Holterhus 1, L Wünsch 2, T Drechsler 3, J Smrcek 4, C Marschke 1, O Hiort 1
  • 1Departments of Pediatrics, UKSH Campus Lübeck, Clinical Research Group “Intersexuality – From Gene to Gender“, Lübeck, Germany
  • 2Pediatric Surgery, UKSH Campus Lübeck, Germany
  • 3Urology, UKSH Campus Lübeck, Germany
  • 4Gynecology, UKSH Campus Lübeck, Germany

Expression of the sexual phenotype of an individual is strongly influenced by sex steroid profiles. Little is known about the individual- and tissue-specific steroid formation and metabolism of normal humans and of individuals with somato-sexual differentiation disorders. The 17β-hydroxysteroid dehydrogenases (17β-HSD)- and the 5α-reductase (5αR)- isoenzymes play an essential role in the synthesis and metabolism of sex steroids. Because of their organ-specific regulating influences of steroid action we investigated the expression-profiles of 17β-HSD- and 5αR-isoenzymes. By analyzing the messenger ribonucleic acid (mRNA) expression of the 17β-HSD-isoenzymes (type 1, 2, 3, 4, 5, 7, 10) and the 5αR-enzymes type 1 and 2 in different tissues of healthy and of individuals with somato-sexual differentiation disorders, we are looking for possible coherences between steroid enzyme expression and sexual phenotypic effects. Methods: Total RNA of four tissues was extracted: genital- (GSF) (healthy males, and persons with hypospadia), scrotal- (SSF), ovarial fibroblasts (OF), and blood samples (healthy males and females). Relative quantification of the different mRNA-transcription was achieved by real-time reverse transcription-PCR with the LightCycler system (Roche). Results: GSF and blood show a tissue-specific transcription profile. In SSF and OF the expression pattern was similar. Some of the investigated GSF-hypospadia samples show significant lower transcription of the 17β-HSD type 5 (p<0,01). No sex- or age-specific regulation of mRNA-expression could be demonstrated. Conclusions: The results show three different tissue-specific transcription-profiles. Differences in the gene-expression of patients with somato-sexual differentiation disorders demonstrate the importance of the enzymes. Future investigations of specific steroid regulated target genes will lead to further understanding of steroid metabolism and action which may have consequences for the different sexual phenotypic expression also in genital malformations.