Expression of the p53 and Wilms' tumor suppressor genes in the rat ovary: gonadotropin repression in vivo and immunohistochemical localization of nuclear p53 protein to apoptotic granulosa cells of atretic follicles

We have previously demonstrated that the gonadotropin-mediated inhibition of apoptosis in ovarian granulosa cells is linked to changes in the expression of several cell death-related genes, including members of the bcl-2 gene family (bcl-2, bax, and bcl-x). Recently, the product of the p53 tumor suppressor gene, a protein reported to play a critical role in regulating cell proliferation and death, has been shown to directly modulate the transcriptional activity of the bcl-2 and bax genes. In addition, the actions of p53 may be amplified through a cooperative interaction with another tumor suppressor protein, the product of the Wilms' tumor suppressor gene (WT-1). Based on our identification of a potential role for bcl-2-related factors in regulating granulosa cell apoptosis and the reported function of p53 as a regulator of bcl-2 and bax gene transcription in extragonadal cells, the present studies were conducted to determine whether the p53 and WT-1 genes are expressed and gonadotropin regulated in the r...