Neonatal exposure to estrogens suppresses activin expression and signaling in the mouse ovary
Neonatal exposure to estrogens suppresses activin expression and signaling in the mouse ovary
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DOI：
10.1210/en.2006-1083
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发表时间：
2007-05-01
期刊：
影响因子：
4.8
通讯作者：
Mayo, Kelly E.
中科院分区：
文献类型：
--
作者：
Kipp, Jingjing L.;Kilen, Signe M.;Mayo, Kelly E.
在卵巢中，类固醇激素雌激素和tgf - β超家族成员激活素都是由颗粒细胞产生的，它们都具有卵巢内功能。新出现的证据表明这两种信号通路相互作用。基于雌激素和激活素对早期卵泡形成和发育的影响，我们假设雌激素治疗可能会改变新生儿卵巢中的激活素信号。因此，本研究旨在探讨新生儿暴露于己烯雌酚（DES）和雌二醇（E-2）对小鼠卵巢激活素信号关键因子mRNA和蛋白水平的影响。CD-1小鼠出生后第1 ~ 5天每天注射DES、E-2或油，第19天采集卵巢和血清。新生儿暴露于DES或E-2可减少小窦卵泡数量，诱导多卵卵泡形成，并降低激活素β亚基mRNA和蛋白水平。与β亚基表达的局部缺失一致，激活素依赖信号的标记物Smad 2的磷酸化在雌激素处理的卵巢中降低。β -亚基表达降低导致血清抑制素水平降低，FSH相应升高。雌激素还能抑制激活素亚基基因启动子的活性，提示其具有直接的转录作用。总之，本研究表明激活素亚单位是雌激素在小鼠卵巢早期作用的靶点。
In the ovary, the steroid hormone estrogen and the TGF-beta superfamily member activin are both produced by granulosa cells and they both have intraovarian functions. Emerging evidence has indicated an interaction of these two signaling pathways. Based on the fact that estrogen and activin can impact early follicle formation and development, we hypothesize that estrogen treatment may alter activin signaling in the neonatal ovary. Therefore, this study was designed to examine the effect of neonatal diethylstilbestrol ( DES) and estradiol (E-2) exposure on the mRNA and protein levels of the key factors involved in activin signaling in the mouse ovary. CD-1 mouse pups were given daily injections of DES, E-2, or oil on postnatal d 1 - 5, and ovaries and sera were collected on d 19. Neonatal DES or E-2 exposure decreased the number of small antral follicles, induced multioocytic follicle formation, and decreased activin beta-subunit mRNA and protein levels. Consistent with local loss of beta-subunit expression, the phosphorylation of Smad 2, a marker of activin-dependent signaling, was decreased in the estrogen-treated ovaries. The decreased beta-subunit expression resulted in a decrease in serum inhibin levels, with a corresponding increase in FSH. Estrogen also suppressed activin subunit gene promoter activities, suggesting a direct transcriptional effect. Overall, this study demonstrates that activin subunits are targets of estrogen action in the early mouse ovary.