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Estrogen Receptors and Estrogen-Metabolizing Enzymes in Human Ovaries during Fetal Development

Departments of Obstetrics and Gynecology (T.E.V., M.M., A.L., J.S.T.) and Pathology (T.E.V., M.M., A.L., R.H., J.S.T.) and Research Center for Molecular Endocrinology, World Health Organization Collaborating Centre for Research on Reproductive Health, and Biocenter Oulu (S.T., O.O., V.I.), University of Oulu, FI-90014 Oulu, Finland

Address all correspondence and requests for reprints to: Juha S. Tapanainen, M.D., Ph.D., Department of Obstetrics and Gynecology, FI-90014 University of Oulu, Finland. E-mail: juha.tapanainen{at}oulu.fi.

Estrogen action plays a crucial role in many processes throughout the human life span, including development. Estrogens are pivotal in the regulation of female reproduction, but little is known about their role during ovarian development. To better understand estrogen action during ovarian development, the expression of estrogen receptors (ERs)- and -ß and key enzymes regulating estradiol production, 17ß-hydroxysteroid dehydrogenases (17HSDs) types 1, 2, and 7, were analyzed in human fetal ovaries. The expression of ERs was related to the development of ovarian follicles. Before the 26th week of fetal life ER was only occasionally detected, but from then onward, its expression was detected in ovarian follicles. Consistent expression of ERß was seen from the 20th week until term. Both ER and ERß were localized to the granulosa cells and oocytes. Expression of 17HSD1 and 17HSD7 enzymes, catalyzing the conversion of estrone to more active estradiol, was detected as early as at the 17th week of fetal life. The expression of 17HSD1 displayed a pattern similar to that of ERs and increased toward term, whereas that of 17HSD7 decreased and was negative by the 36th week. 17HSD1 was localized to the granulosa cells, whereas 17HSD7 expression was more diffuse and was found in both granulosa and stromal cells. 17HSD2, converting estradiol to less potent estrone, was negative in all samples studied. The simultaneous appearance of estrogen-converting enzymes and ERs at the time of follicle formation indicates that the machinery for estrogen action exists in fetal ovaries and suggests a possible role for estrogens in the developing ovary.

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