Human glutathione S‐transferase A ( GSTA ) family genes are regulated by steroidogenic factor 1 (SF‐1) and are involved in steroidogenesis
2013; Wiley; Volume: 27; Issue: 8 Linguagem: Inglês
10.1096/fj.12-222745
ISSN1530-6860
AutoresTakehiro Matsumura, Yoshitaka Imamichi, Tetsuya Mizutani, Yunfeng Ju, Takashi Yazawa, Shinya Kawabe, Masafumi Kanno, Tadayuki Ayabe, Noriyuki Katsumata, Maki Fukami, Masaru Inatani, Yoshio Akagi, Akihiro Umezawa, Tsutomu Ogata, Kaoru Miyamoto,
Tópico(s)Estrogen and related hormone effects
ResumoSteroidogenic factor 1 (SF-1) is a master regulator for steroidogenesis. In this study, we identified novel SF-1 target genes using a genome-wide promoter tiling array and a DNA microarray. SF-1 was found to regulate human glutathione S-transferase A (GSTA) family genes (hGSTA1–hGSTA4), a superfamily of detoxification enzymes clustered on chromosome 6p12. All hGSTA genes were up-regulated by transduction of SF-1 into human mesenchymal stem cells, while knockdown of endogenous SF-1 in H295R cells down-regulated all hGSTA genes. Chromatin immunoprecipitation assays, however, revealed that SF-1 bound directly to the promoters of hGSTA3 and weakly of hGSTA4. Chromosome conformation capture assays revealed that the coordinated expression of the genes was based on changes in higher-order chromatin structure triggered by SF-1, which enables the formation of long-range interactions, at least between hGSTA1 and hGSTA3 gene promoters. In steroidogenesis, dehydrogenation of the 3-hydroxy group and subsequent Δ5-Δ4 isomerization are thought to be enzymatic properties of 3β-hydroxysteroid dehydrogenase (3β-HSD). Here, we demonstrated that, in steroidogenic cells, the hGSTA1 and hGSTA3 gene products catalyze Δ5-Δ4 isomerization in a coordinated fashion with 3β-HSD II to produce progesterone or Δ4-androstenedione from their Δ5-precursors. Thus, hGSTA1 and hGSTA3 gene products are new members of steroidogenesis working as Δ5-Δ4 isomerases.—Matsumura, T., Imamichi, Y., Mizutani, T., Ju, Y., Yazawa, T., Kawabe, S., Kanno, M., Ayabe, T., Katsumata, N., Fukami, M., Inatani, M., Akagi, Y., Umezawa, A., Ogata, T., Miyamoto, K., Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis. FASEB J. 27, 3198–3208 (2013). www.fasebj.org
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