Tissue specific and cyclic expression of insulin-like growth factor binding proteins-1,-2,-3,-4,-5,-6 in the rat oviduct

Although much is known about the expression insulin-like growth factors (IGF) and their receptors in the murine oviduct, significantly less is known about the expression of IGF binding proteins (IGFBPs). To fill this gap in our knowledge, we identified and characterized the tissue specific expression of IGFBP-1 to-6 in rat oviducts over the estrous cycle byin situ hybridization and immunocytochemistry. Tissues were analysed on proestrus (P1000 h, P2000 h), estrus (E0200, E1000 h), and diestrus I and II (DI 1100 h, DII 1100 h). IGFBP-1 was undetectable in the oviduct over the cycle. IGFBP-2 was selectively expressed in the luminal epithelium. The mRNA levels were high between P2000 h and E1000 h but low or undetectable thereafter. Immunoreactive IGFBP-2 was strong to very strong in these cells over most of the cycle. IGFBP-3 mRNA was undetectable in the oviduct; however, strong hybridization and immunoreactive signals were present in the mesosalpinx and mesotubarium, particularly at DI and DII. IGFBP-4 mRNA was not detected in the oviduct. In contrast, immunoreactive IGFBP-4 was observed in the luminal epithelium and the intensity was very strong after ovulation (E1000 h, DI and DII). IGFBP-5 and-6 mRNAs were selectively expressed in circular smooth muscle cells. Hybridization signals were evident over the cycle, but were greatest at estrus. By comparison, IGFBP-5 and-6 proteins were essentially undetectable in these cells except at DII 1100 h when immunostaining was moderate to high. Luminal epithelial cells were weakly positive for IGFBP-5 and-6. However, intense immunostaining was associated with the ciliated border and the luminal fluid juxtaposed to these cells during the cycle. The oocyte-cumulus complexes were immunostained intensely for IGFBP-2,-4,-5 and-6, but their mRNAs were undetectable. The signals were strongest in degenerating cumulus cells suggesting a potential role for these IGFBPs in cumulus apoptosis. These results demonstrate that the estrous cycle is accompanied by major changes in the pattern of expression of IGFBP-2,-4,-5 and-6 in the rat oviduct. We therefore conclude that the regulated production of these particular IGFBPs may be functionally important in modulating IGF activities in the oviduct, oocyte cumulus complexes, and perhaps the preimplantation embryo as well.