Jih M H, Lu J K, Wan Y J, Wu T C
Department of Obstetrics and Gynecology, UCLA School of Medicine 90024.
Biol Reprod. 1993 Dec;49(6):1208-14. doi: 10.1095/biolreprod49.6.1208.
The persistent-estrous (PE) state in aging rats, characterized by a lack of ovulation and absence of estrous cycles, is associated with enhanced inhibin alpha and beta A subunit mRNA expression in the ovaries. It has been shown that the PE state can be interrupted by successive treatments with a progesterone implant (P-implant) and that estrous cycles can be transiently restored after implant removal. The present study examined whether restoration of estrous cycles in PE rats could reverse the altered ovarian inhibin alpha and beta A subunit gene expression. PE rats were treated with subcutaneous P-implants for 6 wk. After implant removal, the return of estrous cyclicity was confirmed by characteristic cyclic changes in vaginal cytology. Ovaries collected from the P-implant-treated animals at 1100 h on diestrus Day 2 or proestrus showed significantly decreased levels of both inhibin alpha and beta A subunit mRNAs compared to those of PE controls and young cyclic females. In situ hybridization revealed that the decreased inhibin alpha subunit mRNA after P-implants was due to decreased gene expression in the granulosa cells of large preovulatory follicles and to a compete absence of gene expression in large, cystic follicles devoid of granulosa cells and oocytes. In addition, inhibin alpha subunit mRNA was expressed in the newly developed follicles after implant removal. The beta A subunit mRNA was detected only in maturing follicles, not in newly developing follicles or in the large cystic follicles. The patterns of ovarian inhibin alpha and beta A subunit gene expression mimicked those of cyclic animals. These data indicate that loss of estrous cycles in aging rats results in an overexpression of inhibin alpha and beta A mRNAs in large and anovulatory follicles and that reinstatement of ovarian cycles in aged rats restores inhibin gene expression to normal levels.
衰老大鼠的持续发情（PE）状态，其特征为缺乏排卵且无发情周期，与卵巢中抑制素α和βA亚基mRNA表达增强有关。研究表明，连续给予孕酮植入物（P-植入物）可中断PE状态，且移除植入物后发情周期可短暂恢复。本研究检测了PE大鼠发情周期的恢复是否能逆转卵巢抑制素α和βA亚基基因表达的改变。对PE大鼠皮下植入P-植入物，持续6周。移除植入物后，通过阴道细胞学特征性的周期性变化确认发情周期恢复。在动情周期第2天的间情期或发情前期11:00采集P-植入物处理动物的卵巢，与PE对照组和年轻的有发情周期的雌性大鼠相比，抑制素α和βA亚基mRNA水平均显著降低。原位杂交显示，P-植入物处理后抑制素α亚基mRNA水平降低是由于排卵前大卵泡颗粒细胞中基因表达减少以及缺乏颗粒细胞和卵母细胞的大的囊性卵泡中完全没有基因表达。此外，移除植入物后，抑制素α亚基mRNA在新发育的卵泡中表达。βA亚基mRNA仅在成熟卵泡中检测到，在新发育的卵泡或大的囊性卵泡中未检测到。卵巢抑制素α和βA亚基基因表达模式与有发情周期的动物相似。这些数据表明，衰老大鼠发情周期的丧失导致大的无排卵卵泡中抑制素α和βA mRNA过度表达，而老龄大鼠卵巢周期的恢复可使抑制素基因表达恢复到正常水平。
