Insulin-like growth factor receptor gene expression in the rat ovary: Divergent regulation of distinct receptor species

Abstract

The intraovarian insulin-like growth factor (IGF) system constitutes a triad composed of ligands, receptors, and binding proteins. Although conventional radioligand receptor assays have documented the presence of specific receptors for insulin and insulin-like peptides in some rat somatic ovarian cell types, the exact cellular localization and hormonal regulation of the receptors in question remain matters of inquiry. To reevaluate the very presence, cellular localization, and hormonal regulation of the IGF receptor gene family in the rat ovary, solution hybridization/RNase protection assays were used wherein ovarian total RNA (20 μg) from immature (21-23 days old) rats was hybridized with 32P-labeled type I IGF receptor, type II IGF/mannose-6-phosphate receptor, and insulin receptor riboprobes. Single protected fragments 261 (type I IGF receptor), 500 (type II IGF/mannose-6-phosphate receptor), and 478 (insulin receptor) bases long were evident in whole ovary, granulosa, and theca-interstitial cells. Hypophysectomy of immature rats led to significant (P < 0.05) albeit variable decrements in the relative (densitometrically quantified) ovarian abundance of transcripts corresponding to the type I IGF (but not insulin or type II IGF/mannose-6-phosphate) receptor. Treatment of immature hypophysectomized rats with FSH (10 μg/rat-day × 2.5 days) resulted in a significant (P < 0.05) increase (4-fold) in transcripts corresponding to the type I IGF receptor in both whole ovarian material and freshly isolated granulosa cells. Similar (3.7-fold) increments (P < 0.05) were noted after treatment with a dieth-ylstilbestrol-containing se silastic implant applied for a total of 5 days. In contrast, treatment with either FSH or diethylstilbestrol was without effect on the relative abundance of whole ovarian transcripts corresponding to the the type II IGF/mannose-6-phosphate or insulin receptor. Taken together, these findings document the ovarian granulosa and thecainterstitial cells as sites of type I IGF receptor, type II IGF/mannose-6-phosphate receptor, and insulin receptor gene expression. Moreover, our present observations reveal a differential pattern of hormonal regulation wherein the ovarian type I IGF (but not the type II IGF/mannose-6-phosphate or insulin) receptor displays gonadotropin as well as estrogen dependence. As such, these observations document the ovarian expression of all members of the IGF receptor family while highlighting the exclusive hormonal responsiveness of type I IGF receptors, whose dynamic involvement in the ovarian life cycle has been previously proposed.