Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2,are expressed in human ovary and sex cord-derived ovarian tumors

Previous studies have implicated transcription factors GATA-4 and GATA-6 in the regulation of murine ovarian development and function. In rodents, GAT A-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 amount s in theca cells and interstitial cells. We have now examined the expressio n 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 immunohis tochemistry 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 folli cles. Both human ovarian tissue samples and freshly isolated GL cells deriv ed from preovulatory follicles of gonadotropin-treated women express GATA-4 , GATA-6, and FOG-2 transcripts, and GATA-6 mRNA expression in GL cell cult ures is stimulated by human CG and 8-bromo-cAMP. The vast majority of granu losa and theca cell tumors examined expressed GATA-4 and GATA-6. We also fo und that mRNA for FOG-2, a recently discovered regulator of GATA-4, is coex pressed 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 F OG-2 are expressed in human ovary and in granulosa and theca cell tumors. O ur findings support a role for GATA-binding proteins in human ovarian folli culogenesis. Moreover, these data suggest that GATA factors may contribute to the phenotypes of sex cord-derived ovarian tumors.