tailieunhanh - Báo cáo khoa học: CYP7B1-mediated metabolism of dehydroepiandrosterone and 5a-androstane-3b,17b-diol – potential role(s) for estrogen signaling

CYP7B1, a cytochrome P450 enzyme, metabolizes several steroids involved in hormonal signaling including 5a-androstane-3b,17b-diol (3b-Adiol), an estrogen receptor agonist, and dehydroepiandrosterone, a precursor for sex hormones. Previous studies have suggested that CYP7B1-dependent metab-olism involving dehydroepiandrosterone or 3b-Adiol may play an impor-tant role for estrogen receptor b-mediated signaling. | ễFEBS Journal CYP7B1-mediated metabolism of dehydroepiandrosterone and 5a-androstane-3p 17p-diol - potential role s for estrogen signaling Hanna Pettersson1 Lisa Holmberg1 Magnus Axelson2 and Maria Norlin1 1 Department of PharmaceuticalBiosciences Division of Biochemistry University of Uppsala Sweden 2 Department of ClinicalChemistry Karolinska Hospital Stockholm Sweden Keywords cytochrome P450 estrogen receptor hydroxylase sex hormone steroid metabolism Correspondence M. Norlin Department of Pharmaceutical Biosciences Division of Biochemistry University of Uppsala Box 578 S-751 23 Uppsala Sweden Fax 46 18 558 778 Tel 46 18 471 4331 E-mail Received 19 December 2007 revised 13 February 2008 accepted 14 February 2008 doi CYP7B1 a cytochrome P450 enzyme metabolizes several steroids involved in hormonal signaling including 5a-androstane-3b 17b-diol 3b-Adiol an estrogen receptor agonist and dehydroepiandrosterone a precursor for sex hormones. Previous studies have suggested that CYP7B1-dependent metabolism involving dehydroepiandrosterone or 3p-Adiol may play an important role for estrogen receptor b-mediated signaling. However conflicting data are reported regarding the influence of different CYP7B1-related steroids on estrogen receptor b activation. In the present study we investigated CYP7B1-mediated conversions of dehydroepiandrosterone and 3b-Adiol in porcine microsomes and human kidney cells. As part of these studies we compared the effects of 3b-Adiol a CYP7B1 substrate and 7a-hydroxy-dehydroepiandrosterone a CYP7B1 product on estrogen receptor b activation. The data obtained indicated that 3b-Adiol is a more efficient activator thus lending support to the notion that CYP7B1 catalysis may decrease estrogen receptor b activation. Our data on metabolism indicate that the efficiencies of CYP7B1-mediated hydroxylations of dehydroepiandrosterone and 3b-Adiol are very similar. The enzyme catalyzed both .