A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary

被引:134
作者
Cheng, GJ
Zhang, WH
Mäkinen, S
Saji, S
Warner, M
Gustafsson, JÅ [1 ]
Hovatta, O
机构
[1] Novum, Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden
[2] Novum, Karolinska Inst, Dept Biosci, S-14186 Huddinge, Sweden
[3] Huddinge Univ Hosp, Karolinska Inst, Dept Obstet & Gynaecol, S-14186 Huddinge, Sweden
[4] Univ Turku, Inst Biomed, Dept Anat, FIN-20520 Turku, Finland
关键词
androgen receptor; courpus luteum; estradiol receptor; follicular development; granulosa cells; ovary; ovulation;
D O I
10.1095/biolreprod66.1.77
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Estrogen receptor beta (ERP) is highly expressed, but ER alpha is not detectable in granulosa cells in the mouse ovary. In ER beta knockout (BERKO) mice, there is abnormal follicular development and very reduced fertility. At 3 wk of age, no significant morphologic differences were discernible between wild type (WT) and BERKO mouse ovaries, but by 5 mo of age, atretic follicles were abundant in BERKO mice and there were very few healthy late antral follicles or corpora lutea. At 2 yr of age, unlike the ovaries of their WT littermates, BERKO mouse ovaries were devoid of healthy follicles but had numerous large, foamy lipid-filled stromal cells. The late antral and atretic follicles in BERKO mice were characterized by a high level of expression of the androgen receptor (AR) and IGF-1 receptor. These proteins were abundantly expressed in granulosa cells of preantral and early antral follicles in both genotypes, but their expression was extinguished in late antral follicles of WT mice. Healthy late antral follicles and corpora lutea were restored in BERKO ovaries after 15 days of treatment of mice with the antiandrogen flutamide. The results suggest that in the absence of ER beta there was a loss of regulation of AR. Because androgens enhance recruitment of primordial follicles into the growth pool and cause atresia of late antral follicles, the inappropriately high level of AR probably is related to the follicular atresia and to the early exhaustion of follicles in BERKO mice.
引用
收藏
页码:77 / 84
页数:8
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