Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production
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Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production Yoshihiko Inaoka1, Takashi Yazawa1, Tetsuya Mizutani1, Koichi Kokame2, Kenji Kangawa2, Miki Uesaka1, Akihiro Umezawa3 and Kaoru Miyamoto*1 Address: 1Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan, 2National Cardiovascular Research Center, Osaka 565-8565, Japan and 3National Research Institute for Child Health and Development, Tokyo 157-8535, Japan Email: Yoshihiko Inaoka - [email protected]; Takashi Yazawa - [email protected]; Tetsuya Mizutani - [email protected]; Koichi Kokame - [email protected]; Kenji Kangawa - [email protected]; Miki Uesaka - [email protected]; Akihiro Umezawa - [email protected]; Kaoru Miyamoto* - [email protected] * Corresponding author
Published: 16 December 2008 Reproductive Biology and Endocrinology 2008, 6:62
doi:10.1186/1477-7827-6-62
Received: 6 October 2008 Accepted: 16 December 2008
This article is available from: http://www.rbej.com/content/6/1/62 © 2008 Inaoka et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: P450 oxidoreductase (POR) catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS), and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs) differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis. Methods: Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcriptionpolymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E) POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells. Results: POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for ar
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