Cellular pattern of insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the developing and mature ovarian follicle

Abstract

We have employed in situ hybridization histochemistry to map the cellular pattern of insulin-like growth factor-I (IGF-I) and the IGF-I receptor gene expression in developing rat ovaries from the time of birth through adulthood, and in response to hypophysectomy and gonadotropin replacement. From the early postnatal period, both IGF-I and IGF-I receptor messenger RNAs (mRNAs) were highly abundant and evenly distributed in granulosa cells of small, growing follicles. In large follicles, however, IGF-I gene expression was heterogeneous. IGF-I mRNA was most abundant in granulosa cells lining the antrum and surrounding the oocyte, but was low or undetectable in mural granulosa cells of Graafian follicles, and was also undetectable in luteinized granulosa cells of corpora lutea. IGF-I receptor mRNA was evenly distributed in developing and mature follicles and was highly abundant in the luteinized granulosa cells of corpora lutea. IGF-I receptor but not IGF-I mRNA was detected in growing oocytes. Hypophysectomy resulted in a decrease and treatment with PMSG resulted in an increase in follicular IGF-I receptor mRNA levels, whereas there was no change in IGP-I mRNA levels in the same protocol. In summary, high levels of both IGF-I and IGF-I receptor gene expression occur in the granulosa cells of actively growing follicles, suggesting that granulosa cell IGF-I may have a role in follicular or oocyte growth. IGF-I gene expression is lost concomitant with follicular enlargement and granulosa cell differentiation, whereas IGF-I receptor gene expression continues at high levels in luteinized granulosa cells, suggesting that IGF effects on differentiated granulosa cell function are due to circulating, not local, hormone. Finally, granulosa cell IGF-I receptor gene expression appears to be regulated by the gonadotropin present in pregnant mare serum.