Insulin-like growth factor binding proteins show distinct patterns of expression in the rat uterus

An intrinsic insulin-like growth factor (IGF) system, complete with IGF ligands, receptors, and biological responses, is present in the rat uterus, where it is thought to regulate uterine homeostasis by autocrine/paracrine mechanisms. It is known that IGF binding proteins (IGFBP) modulate IGF-I and IGF-II action, but very little information is available 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 localized only in the luminal epithelium of the endometrium. It was abundant 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 localized 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 endometrium. It was moderately abundant at diestrus I and II, but the signal was very low or absent at other times in the cycle. IGFBP-5 mRNA was localized in the circular and longitudinal muscle layers of the myometrium. The IGFBP-5 hybridization signal was maximal at diestrus, weak on proestrus, and moderate during estrus. IGFBP-6 mRNA was also expressed in the myometrium. The signal was strong on estrus morning (E0200 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 uterus. 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-specific expression of IGFBP-2 to -6 may be involved in modulating the activity of the IGF ligands during the proliferative and secretory phases of the uterine cycle.