TISSUE-SPECIFIC AND CYCLIC EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1, PROTEIN-2, PROTEIN-3, PROTEIN-4, PROTEIN-5, PROTEIN-6 IN THE RAT OVIDUCT

Although much is known about the expression insulin-like growth factor s (ICF) and their receptors in the murine oviduct, significantly less is known about the expression of ICF binding proteins (IGFBPs). To fil l this gap in our knowledge, we identified and characterized the tissu e specific expression of IGFBP-1 to -6 in rat oviducts over the estrou s cycle by in situ hybridization and immunocytochemistry. Tissues were analysed on proestrus (P1000 h, P2000 h), estrus (E0200, E1000 h), an d 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 th e luminal epithelium. The mRNA levels were high between P2000 h and E1 000 h but low or undetectable thereafter. Immunoreactive IGFBP-2 was s trong to very strong in these cells over most of the cycle. IGFBP-3 mR NA was undetectable in the oviduct; however, strong hybridization and immunoreactive signals were present in the mesosalpinx and mesotubariu m, particularly at DI and DII. IGFBP-4 mRNA was not detected in the ov iduct. 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 circ ular smooth muscle cells. Hybridization signals were evident over the cycle, but were greatest at estrus. By comparison, IGFBP-5 and -6 prot eins were essentially undetectable in these cells except at DII 1100 h when immunostaining was moderate to high. Luminal epithelial cells we re weakly positive for IGFBP-5 and -6. However, intense immunostaining was associated with the ciliated border and the luminal fluid juxtapo sed to these cells during the cycle. The oocyte-cumulus complexes were immunostained intensely for IGFBP-2, -4, -5 and -6, but their mRNAs w ere undetectable. The signals were strongest in degenerating cumulus c ells suggesting a potential role for these IGFBPs in cumulus apoptosis . These results demonstrate that the estrous cycle is accompanied by m ajor 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.