Dam Phuong T M, Jang You-Jee, Kim Ja-Yeon, Choi Seul-Gee, Park Jae-Il, Seo Young-Woo, Chun Sang-Young
School of Biological Sciences and Biotechnology, Faculty of Life Science, Chonnam National University, Gwangju 500-757, Republic of Korea.
Animal Facility of Aging Science, Korea Basic Science Institute, Gwangju 61186, Republic of Korea.
Endocr J. 2017 Aug 30;64(8):797-805. doi: 10.1507/endocrj.EJ17-0038. Epub 2017 Jul 11.
The potent androgen 5α-dihydrotestosterone is metabolized to the weak androgen 5α-androstane-3α, 17β-diol (3α-diol) by the enzyme aldo-keto reductase family 1, member C14 (Akr1c14) in rodents. The purpose of the present study was to investigate the regulation of Akr1c14 expression during the ovulatory process in rat ovaries. Northern blot analysis revealed that treatment of immature rats with equine chorionic gonadotropin resulted in lowered Akr1c14 expression, whereas subsequent treatment with human chorionic gonadotropin (hCG) increased ovarian Akr1c14 expression within 3 h. In situ hybridization analysis showed that Akr1c14 mRNA was localized in granulosa cells of growing follicles before hCG treatment, but it was also expressed in granulosa cells of preovulatory follicles after hCG treatment. Akr1c14 protein expression increased after 6 h of hCG treatment and was sustained at high levels until 12 h. The levels of 3α-diol in preovulatory follicles isolated from ovaries in vivo were fluctuated by hCG treatment; decreased at 6 h and increased at 9 h. Human CG-induced Akr1c14 expression was suppressed by treatment with the progesterone receptor antagonist RU486, but not with the cyclooxygenase inhibitor indomethacin. Taken together, these findings demonstrate the induction of Akr1c14 by hCG in granulosa cells of rat preovulatory follicles that was regulated by progesterone receptor antagonist.
在啮齿动物中,强效雄激素5α-双氢睾酮被醛酮还原酶家族1成员C14(Akr1c14)代谢为弱雄激素5α-雄烷-3α,17β-二醇(3α-二醇)。本研究的目的是调查大鼠卵巢排卵过程中Akr1c14表达的调控情况。Northern印迹分析显示,用马绒毛膜促性腺激素处理未成熟大鼠会导致Akr1c14表达降低,而随后用人绒毛膜促性腺激素(hCG)处理会在3小时内增加卵巢Akr1c14的表达。原位杂交分析表明,hCG处理前,Akr1c14 mRNA定位于生长卵泡的颗粒细胞中,但hCG处理后,排卵前卵泡的颗粒细胞中也有表达。hCG处理6小时后,Akr1c14蛋白表达增加,并持续高水平表达直至12小时。体内从卵巢分离的排卵前卵泡中3α-二醇的水平受hCG处理的影响而波动;6小时时降低,9小时时升高。人绒毛膜促性腺激素诱导的Akr1c14表达被孕酮受体拮抗剂RU486处理所抑制,但不被环氧化酶抑制剂吲哚美辛抑制。综上所述,这些发现表明hCG在大鼠排卵前卵泡颗粒细胞中诱导Akr1c14表达,且该过程受孕酮受体拮抗剂调控。