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Regular Article |
a Departments of Medical Nutrition and
b Biosciences, Karolinska Institute, NOVUM, S-14186 Huddinge, Sweden
c Department of Obstetrics and Gynaecology, Huddinge University Hospital, Karolinska Institute, S-14186 Huddinge, Sweden
d Department of Anatomy, Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland
Estrogen receptor beta (ERß) is highly expressed, but ER
is not detectable in granulosa cells in the mouse ovary. In ERß knockout (BERKO) mice, there is abnormal follicular development and very reduced fertility. At 3 wk of age, no significant morphologic differences were discernable 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 ERß 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.
1 Supported by grants from KaroBio AB, the Swedish Cancer Fund, and the Swedish Medical Research Council. S.S. has a fellowship from the Wenner-Gren Foundation and a research grant from the Scandinavia-Japan Sasakawa Foundation.
2 Correspondence: Jan-Åke Gustafsson, Department of Medical Nutrition, Karolinska Institute, NOVUM, S-14186, Huddinge, Sweden. FAX: 46 8 779 87 95; jan-ake.gustafsson{at}mednut.ki.se
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