THE MOUSE INTRAOVARIAN INSULIN-LIKE-GROWTH-FACTOR-I SYSTEM - DEPARTURES FROM THE RAT PARADIGM

Although the rat intraovarian insulin-like growth factor I (IGF-I) sys tem is well documented, the increasing availability of null mouse muta nts for components of the IGF system necessitates characterization of the mouse model as well. Therefore, we undertook to define the compone nts of the mouse intraovarian IGF-I system and to examine its operatio nal characteristics. The cellular pattern of ovarian gene expression w as comparable in the immature rat and mouse for IGF-I and the type I I GF receptor. In both species, IGF-I messenger RNA (mRNA) is selectivel y expressed by granulosa cells in growing, healthy appearing follicles . Type I IGF receptor mRNA was also concentrated in granulosa cells, b ut was uniformly expressed in all follicles large and small, healthy a nd atretic appearing alike. Cellular patterns of IGF-binding protein ( IGFBP) gene expression were similar in mouse and rat, except in the ca se of IGFBP-2. IGFBP-2 mRNA was localized to the mouse granulosa cell, in contrast to its concentration in the rat thecal-interstitial compa rtment. This difference in IGFBP expression pattern was also noted in cultured mouse and rat granulosa cells. Although immunoreactive IGFBP- 4 (24 and 28 kDa) and IGFBP-5 (29 kDa) were shared by both species, th e cultured mouse granulosa cell also featured immunoreactive IGFBP-2 ( 30 kDa). The mouse paradigm further differed from its rat counterpart in that a maximal dose of FSH, previously shown to suppress the elabor ation of rat granulosa cell-derived IGFBPs, was without effect. The ad dition of IGF-I proved stimulatory to the accumulation of the 28- to 2 9-kDa IGFBPs, as previously reported for the rat. However, IGF-I prove d inhibitory to the accumulation of the 24-kDa IGFBP (presumptive nong lycosylated IGFBP-4); no consistent effect was reported for the rat mo del. Functional comparisons of mouse and rat ovarian cell cultures rev ealed qualitatively comparable FSH-stimulated steroidogenesis, disposi tion of radiolabeled pregnenolone, IGF-I-amplified FSH action, and IGF BP-mediated antigonadotropic activity. These findings indicate that th e mouse intrafollicular IGF-I system differs from the rat paradigm in both the makeup and regulation of granulosa cell-derived IGFBPs as wel l as in the intensity and character of the steroidogenic process. Stud ies employing the mouse model must take into account these important d istinctions relative to the more established rat paradigm.