Rat ovarian insulin-like growth factor binding protein-4 : A hormone-dependent granulosa cell-derived antigonadotropin

Objective:To assess the in vivo regulation of ovarian insulin-like growth factor binding protein-4 (GFBP-4) mRNA expression by gonadotropins and estrogen.Methods:Whole varian RNA, obtained from two models of follicular development, was extracted and analyzed by Northern blotting. Immature rats were treated with pregnant mare senum gonadotropin (PMSG) followed 48 hours later with hCG, or alternatively were hypophysectomized and treated with FSH and/or diethylstilbestrol (DES). Localization of IGFBP-4 expression was assessed in the former study by in situ hybridization. Finally, the ability of human IGFBP-4 to antagonize FSH-stimulated progesterone accumulation was assessed in vitro.Results:The ovarian content of IGFBP-4 transcripts increased threefold (P < .05) at 12 hours after PMSG but was near baseline at 24 and 48 hours. The abundance of IGFBP-4 mRNA increased (P < .05) again at 6 and 24 hours after hCG. The expression of IGFBP-4 was localized to granulosa cells of prenatral (untreated) and small antra...