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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 9 3476-3483
Copyright © 2000 by The Endocrine Society

Original Studies

Transcription Factors GATA-4 and GATA-6 and a GATA Family Cofactor, FOG-2, Are Expressed in Human Ovary and Sex Cord-Derived Ovarian Tumors1

Mika P. E. Laitinen2, Mikko Anttonen2, Ilkka Ketola, David B. Wilson, Olli Ritvos, Ralf Butzow and Markku Heikinheimo

Department of Bacteriology and Immunology, Haartman Institute (M.P.E.L., O.R.), Children’s Hospital (M.A., I.K., M.H.), and Department of Obstetrics and Gynecology and Pathology (R.B.), University of Helsinki and Programme for Developmental and Reproductive Biology, Biomedicum (M.P.E.L., M.A., I.K., O.R., M.H.), 00290 Helsinki, Finland; and Departments of Pediatrics (D.B.W., M.H.) and Molecular Biology and Pharmacology (D.B.W.), Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, Missouri 63110

Address correspondence and requests for reprints to: Markku Heikinheimo, M.D., Ph.D., Children’s Hospital, University of Helsinki, Stenbäckinkatu 11, 00290 Helsinki, Finland. E-mail: markku.heikinheimo{at}helsinki.fi

Previous studies have implicated transcription factors GATA-4 and GATA-6 in the regulation of murine ovarian development and function. In rodents, GATA-4 is expressed in granulosa cells of primary and early antral follicles, whereas GATA-6 is expressed in granulosa cells of late antral follicles and luteal glands. Both transcription factors can be detected in lesser amounts in theca cells and interstitial cells. We have now examined the expression of GATA-4 and GATA-6 in human ovaries, human granulosa-luteal (GL) cells and sex cord-derived tumors. We show by in situ hybridization and immunohistochemistry that GATA-4 and GATA-6 messenger RNA (mRNA) and GATA-4 protein are present in granulosa and theca cells in both preantral and antral follicles. Both human ovarian tissue samples and freshly isolated GL cells derived from preovulatory follicles of gonadotropin-treated women express GATA-4, GATA-6, and FOG-2 transcripts, and GATA-6 mRNA expression in GL cell cultures is stimulated by human CG and 8-bromo-cAMP. The vast majority of granulosa and theca cell tumors examined expressed GATA-4 and GATA-6. We also found that mRNA for FOG-2, a recently discovered regulator of GATA-4, is coexpressed with GATA-4 in human ovary samples, normal granulosa cells, and in sex cord-derived tumors. Our results demonstrate that GATA-4, GATA-6, and FOG-2 are expressed in human ovary and in granulosa and theca cell tumors. Our findings support a role for GATA-binding proteins in human ovarian folliculogenesis. Moreover, these data suggest that GATA factors may contribute to the phenotypes of sex cord-derived ovarian tumors.




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