Brca1 is expressed independently of hormonal stimulation in the mouse ovary

BRCA1 mutations lead to cancer susceptibility in hormonally dependent tissues such as the ovary and breast. To test the hypothesis that Brca1 expression in the ovary is hormonally regulated and specifically regulated by a functional estrogen receptor, we examined its expression by in situ hybridization in ovaries from virgin, pregnant, and lactating mice, in hypophysectomized mice treated with hormones, and in estrogen-receptor-deficient mice. To determine the relationship between Brca1 expression and cell cycle, serial and adjacent sections of ovary were evaluated for proliferating cell nuclear antigen by immunohistochemistry. Regardless of the model, Brca1 was consistently expressed in granulosa and thecal cells of follicle populations that proliferate independently of hormonal stimulation. Expression was similar in these same follicle populations in the ovaries of estrogen-receptor-deficient mice, in which the lack of this estrogen receptor results in abnormal and incomplete follicular development. Brca1 expression was diminished in the granulosa and thecal cells of hormonally dependent antral follicles. Brca1 expression was also localized to luteal cells of recently formed corpora lutea and corpora lutea associated with pregnancy, but it was greatly diminished in regressing corpora lutea in cycling mice. In all cases, Brca1 expression correlated to S-phase proliferating cell nuclear antigen nuclear staining. Thus, Brca1 expression in the mouse ovary occurs independently of hormonal status and in the absence of a major estrogen receptor-mediated pathway; it is, however, closely correlated with cell cycle in mouse ovarian granulosa, thecal, and luteal cell.