Nagai Akiko, Ikeda Yayoi, Aso Takeshi, Eto Kazuhiro, Ikeda Masa-Aki
Comprehensive Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
J Med Dent Sci. 2003 Mar;50(1):35-40.
Exposing neonatal rats with the synthetic estrogen, diethylstilbestrol (DES), induces morphological and functional abnormalities in the adult ovary. We examined the events that lead to this condition using female rats that were exposed to DES for the first five days after birth. The expression of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 (P450scc), which are both required for steroidogenesis in the theca/interstitial region was markedly reduced. The expression of Mullerian inhibiting substance (MIS) was transiently increased in small growing follicles in the ovary of DES-treated rats at postnatal day 7 (P7), and the expression profile in the ovary differed between DES- and vehicle oil-treated rats at P14 and P21. The expression of the transcription factor, steroidogenic factor-1 (SF-1), reduced in theca/interstitial cells, but increased in granulosa cells of primary follicles. These results indicate that altered steroidogenesis and MIS production are mechanisms through which DES induces abnormal ovarian development, and support the notion that androgens and MIS are both critical factors in regulating early ovarian differentiation.
用合成雌激素己烯雌酚（DES）处理新生大鼠会导致成年卵巢出现形态和功能异常。我们使用出生后前五天暴露于DES的雌性大鼠，研究了导致这种情况的相关事件。在卵泡膜/间质区域进行类固醇生成所必需的类固醇生成急性调节蛋白（StAR）和胆固醇侧链裂解细胞色素P450（P450scc）的表达显著降低。在出生后第7天（P7），DES处理大鼠卵巢中正在生长的小卵泡中缪勒氏管抑制物质（MIS）的表达短暂增加，并且在P14和P21时，DES处理组和赋形剂油处理组大鼠卵巢中的表达谱有所不同。转录因子类固醇生成因子-1（SF-1）在卵泡膜/间质细胞中的表达降低，但在初级卵泡的颗粒细胞中增加。这些结果表明，类固醇生成和MIS产生的改变是DES诱导卵巢发育异常的机制，并支持雄激素和MIS都是调节早期卵巢分化的关键因素这一观点。
