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Immunolocalization of Nuclear Transcription Factors, DAX-1 and COUP-TF II, in the Normal Human Ovary: Correlation with Adrenal 4 Binding Protein/ Steroidogenic Factor-1 Immunolocalization during the Menstrual Cycle

Department of Pathology (Y.S., T.S., K.H., H.S.), Department of Medicine (Y.S., H.S., S.I.), Division of Nephrology, Endocrinology, and Vascular Medicine, and Department of Obstetrics and Gynecology (K.I.), Tohoku University School of Medicine, Sendai, Japan

Address all correspondence and requests for reprints to: Yoko Sato, M.D., Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail: Yoko21tako{at}aol.com.

Steroid synthesis in the human ovary is regulated by the temporal and spatial expression of enzymes involved in each step of ovarian steroidogenesis. Recent studies have demonstrated that DAX-1 and COUP-TFII negatively regulate adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1)-dependent transcription of steroidogenic enzymes in experimental animals. In this study the expression patterns of these proteins in human normal ovaries were examined using immunohistochemistry and compared with those of steroidogenic enzymes. In the ovarian follicle and corpora lutea, immunoreactive DAX-1 protein was detected predominantly in granulosa cells, whereas COUP-TFII was identified in thecal cells. In granulosa cells, both immunoreactive DAX-1 and Ad4BP/SF-1 protein expression increased after the preantral follicular stage. DAX-1 immunoreactivity was relatively high compared with that of Ad4BP/SF-1 in all follicular stages from premordial to nondominant. The increase in expression of Ad4BP/SF-1 immunoreactivity between follicles in the preantral and dominant stages of follicular development was greater than that in DAX-1 expression. In thecal cells, immunoreactive COUP-TFII was consistently elevated throughout the menstrual cycle, whereas Ad4BP/SF-1 immunoreactivity increased according to the development of the follicle. These results indicated that DAX-1 and COUP-TFII may play a role in the modulation of Ad4BP/SF-1-dependent transcription of steroidogenic enzymes in different cell types and follicular stages in normal cycling human ovaries.

Abbreviations: Ad4BP, Adrenal 4 binding protein; COUP-TFII, chicken ovalbumin upstream promoter-transcription factor II; DAX-1, dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1; 3ß-HSD, 3ß-hydroxysteroid dehydrogenase; LRH-1, liver receptor homolog 1; P450_arom, P450 aromatase; P450_C17, P450 17-hydroxylase; SF-1, steroidogenic factor-1.

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