IMMUNOHISTOCHEMICAL LOCALIZATION OF AD4-BINDING PROTEIN WITH CORRELATION TO STEROIDOGENIC ENZYME EXPRESSION IN CYCLING HUMAN OVARIES AND SEX CORD-STROMAL TUMORS

Ad4-binding protein (Ad4BP) has been demonstrated recently as a transc ription factor that serves as a general regulator of all steroidogenic P450 genes. We examined the expression of Ad4BP in 32 normal cycling human ovaries and 22 human ovarian sex cord stromal tumors by immunobl otting and immunohistochemistry. Immunoblotting of normal cycling huma n ovaries revealed a single band of 53 kilodaltons, corresponding to t he mol wt of Ad4BP. We also correlated Ad4BP expression with the immun olocalization of the steroidogenic enzymes (side-chain cleavage cytoch rome P450, cytochrome P450 17 alpha-hydroxylase, and cytochrome P450 a romatase). Ad4BP immunoreactivity, which was present only in the nucle i, was observed sporadically in the granulosa cells and adjacent strom al cells in the preantral follicles. In the dominant antral follicles, Ad4BP was detected in both granulosa and theca interna cells. However , in the nondominant antral follicles, Ad4BP was observed only in thec a interna cells. In the corpus luteum, Ad4BP was present in both lutei nized granulosa and thecal cells. Ad4BP was also expressed in some atr etic follicles and degenerating corpora lutea. The spatial and tempora l localization of Ad4BP in the normal cycling human ovary generally co rrelated well with that of steroidogenic enzymes. However, expression of the steroidogenic enzymes followed that of Ad4BP during the develop ing stages of the preantral follicle and vice versa during the process of follicular atresia. In ovarian sex cord stromal tumors, Ad4BP expr ession was observed in tumor cells that were positive for steroidogeni c enzymes, but not in nonsteroidogenic tumor cells. These results, esp ecially the in situ colocalization of Ad4BP and the steroidogenic enzy mes, suggest that Ad4BP has the potential to control steroidogenic P45 0 expression in both normal and pathological human ovaries.