The nongenomic actions of estradiol-17β are mediated by transmembrane estrogen receptors. Recently, G protein-coupled receptor 30 (GPR30) has been suggested to be a transmembrane estrogen receptor that can mediate rapid and transcription-independent estradiol-17β signaling in different cell types. However, the expression, regulation, or biological relevance of GPR30 in the ovary remains unknown. We examined the expression and hormonal regulation of GPR30 mRNA and protein in hamster ovarian cells during the estrous cycle and after hypophysectomy and hormone replacement. GPR30 protein expression was high in the theca, appreciable in the granulosa, but low in luteal cells. GPR30 protein levels in granulosa and theca cells increased steadily with the development of preantral and antral follicles, respectively. GPR30 mRNA and protein levels increased significantly on diestrous (d 3 of the estrous cycle), but decreased on d 4 at 1600 h after the LH surge. GPR30 mRNA levels increased significantly after hypophysectomy. Although steroid treatment failed to alter ovarian GPR30 mRNA levels, either FSH or LH effectively reduced the levels. Interestingly, the decrease in GPR30 mRNA corresponded to a marked increase in the receptor protein levels. FSH treatment, either alone or together with LH, resulted in a marked increase in GPR30 immunostaining in granulosa cells. LH alone significantly increased immunostaining in theca cells. These results suggest that GPR30 is expressed in the membrane of hamster granulosa and theca cells, and the expression is regulated by gonadotropins. The unique pattern of GPR30 expression suggests that gonadotropin-regulated follicular cell functions may involve GPR30 activity.
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