Granulosa cell DNA synthesis is strictly correlated with the presence of insulin-like growth factor I and absence of c-fos/c-jun expression.

Abstract

Insulin-like growth factor I (IGF-I) mRNA is selectively expressed by a subset of rat ovarian follicles. To elucidate the biological role and regulation of follicular IGF-I, we have analyzed individual follicles with respect to IGF-I production, DNA synthesis, and c-fos and c-jun expression, since AP-1 complex components have been implicated both in regulation of IGF-I gene expression and cell proliferation. IGF-I mRNA localization, bromodeoxyuridine (BRDU) incorporation, and c-fos and c-jun immunoreactivity were compared in serial sections from prepubertal and mature rat ovaries. BRDU incorporation is exclusively concentrated in IGF-I-expressing follicles in both prepubertal and mature rats, with further intrafollicular correlation between local concentrations of BRDU-positive granulosa cells and IGF-I mRNA. Furthermore, there is a striking negative correlation between IGF-I mRNA localization and follicular fos/jun immunoreactivity. Both c-fos and c-jun are readily detected in granulosa cells of luteinized follicles where IGF-I mRNA is never found. Immunoreactive c-jun but not c-fos is detected in granulosa cells of atretic follicles, while neither c-fos nor c-jun is detected in IGF-I mRNA-positive granulosa cells. These data implicate IGF-I in granulosa cell proliferation and the fos/jun heterodimer in granulosa cell luteinization, while expression of c-jun in the absence of c-fos may be implicated in programmed granulosa cell death.