INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS SHOW DISTINCT PATTERNS OFEXPRESSION IN THE RAT UTERUS

An intrinsic insulin-like growth factor (IGF) system, complete with IG F ligands, receptors, and biological responses, is present in the rat uterus, where it is thought to regulate uterine homeostasis by autocri ne/paracrine mechanisms. It is known that IGF binding proteins (IGFBP) modulate IGF-I and IGF-II action, but very little information is avai lable concerning their cellular localization in the uterus. Therefore, we have employed in situ hybridization to localize IGFBP-1, -2, -3, - 4, -5, and -6 mRNAs in the adult rat uterus during the estrous cycle. IGFBP-1 was undetectable in all uteri examined. IGFBP-2 mRNA was local ized only in the luminal epithelium of the endometrium. It was abundan t during proestrus (P1000 h, P2000 h) and early estrus (E0200 h), but was relatively low at other stages of the cycle. IGFBP-3 mRNA was Loca lized to the stroma cells juxtaposed to the endometrium. A weak signal was detected on estrus morning (E0200 h, E1000 h), but high levels of IGFBP-3 mRNA were observed in the stroma cells on Day 12 of pregnancy . IGFBP-4 mRNA was localized only in the luminal epithelium of the end ometrium. It was moderately abundant at diestrus I and II, but the sig nal was very low or absent at other times in the cycle. IGFBP-5 mRNA w as localized in the circular and longitudinal muscle layers of the myo metrium. The IGFBP-5 hybridization signal was maximal at diestrus, wea k on proestrus, and moderate during estrus. IGFBP-6 mRNA was also expr essed in the myometrium. The signal was strong on estrus morning (E020 0 h and E1000 h) and low or absent at other times in the cycle. These results provide the first direct evidence that the genes encoding the six IGFBP are expressed in a tissue-specific manner in the adult rat u terus. Equally important, the levels of the mRNA for each IGFBP appear to change throughout the estrous cycle, but not in a parallel fashion . These results support the hypothesis that inducible and tissue-speci fic expression of IGFBP-2 to -6 may be involved in modulating the acti vity of the IGF ligands during the proliferative and secretory phases of the uterine cycle.