RELAXIN INCREASES INSULIN-LIKE GROWTH-FACTORS (IGFS) AND IGF-BINDING PROTEINS OF THE PIG UTERUS IN-VIVO

Relaxin promotes growth of reproductive tissues, including the uterus. Although we have evidence of a role for insulin-like growth factor I (IGF-I) in mediating relaxin-induced growth of porcine granulosa cells in vitro, the mechanism of action by which relaxin enhances uterine g rowth has not been identified. To investigate a role for the uterine i nsulin-like growth factor (IGF) system in relaxin-induced uterine grow th, we monitored the effects of relaxin on porcine IGFs and IGF-bindin g proteins (IGFBPs) in vivo. The trophic effects of relaxin on the ute rus were elicited by administering relaxin or saline to prepubertal gi lts every 6 h for 54 h. Three hours after the last injection, uterine flushes, uteri, follicular fluid, and ovaries were collected. Estradio l was measured in plasma and follicular fluid to confirm the prepubert al status of each animal. Significantly higher concentrations of uteri ne lumen IGF-I (P < 0.05) and IGF-II (P < 0.01) were observed in anima ls treated with relaxin. However, relaxin administration did not affec t uterine IGF-I and -II gene expression, as determined by a ribonuclea se protection assay and Northern analysis, respectively. In uterine fl ushes, relaxin treatment increased an IGFBP doublet (33 and 34.5 kDa) and IGFBP-3. The uterine IGFBP doublet was identified as IGFBP-2 by im munoprecipitation. Plasma or follicular fluid IGFs and IGFBPs were una ffected by relaxin administration. In addition, relaxin did not influe nce IGF-I binding to its uterine receptor. This is the first study to demonstrate regulation of the pig uterine IGF system by relaxin. In co nclusion, the data point to IGF-I, IGF-II, IGPBP-2, and IGFBP-3 as put ative mediators of relaxin-induced uterine growth in the pig.