Rat ovarian insulin-like growth factor II gene expression is theca-interstitial cell-exclusive: Hormonal regulation and receptor distribution

While the potential role of insulin-like growth factor (IGF)-I in ovarian physiology has been extensively studied, relatively limited attention has been paid to IGF-II the very presence of which in the mature rat ovary has been questioned. In the present study, we have reevaluated rat ovarian IGF-II gene expression, its cellular localization, hormonal regulation, and site(s) of receptor interaction. IGF-II mRNA was detected in whole ovaries from immature as well as mature intact rats. Cellular localization studies revealed IGF-II transcripts in theca-interstitial but not granulosa cells (a site of IGF-I gene expression). In contrast, no cellular selectivity was noted for Type I and Type II IGF receptor gene expression, both of which were clearly detectable in both granulosa and theca-interstitial cells. In vivo treatment of immature hypophysectomized rats with diethylstilbestrol reduced ovarian IGF-II mRNA levels while increasing IGF-I mRNA levels. Taken together, these and previous observations reveal fundamental differences in the cellular localization and hormonal regulation of ovarian IGF gene expression in that IGF-II gene expression (unlike IGF-I) is theca-interstitial (rather than granulosa) cell-specific, and is subject to down (as opposed to up) regulation in response to estrogenic stimulation. In contrast, Type I and Type II IGF receptors exist on both somatic cell types of the rat ovary. These observations are consistent with the view that IGF-II of theca-interstitial cell origin may not only play an autocrine role but may also serve as one of several signals through which this androgen-producing cell may communicate in a paracrine fashion with the adjacent granulosa cell compartment.