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

We investigated the possible presence of the mRNAs encoding four insulin-like growth factor-binding proteins (IGFBP-1, -2, -3, and -4) in the rat ovary. It has been demonstrated previously by Northern analysis that adult rat ovaries contain mRNA transcripts for IGFBP-2 and -3. Here we show by Northern analysis that adult rat ovaries contain mRNA for IGFBP-4, but the mRNA for IGFBP-1 was below the limit of detection. Using in situ hybridization, IGFBP-1 mRNA was not detected in any of the ovaries tested. The IGFBP-2 mRNA was localized specifically in thecal interstitial cells (TIC) and secondary interstitial cells of all ovaries. The IGFBP-2 signal was very strong in TIC of all Graafian follicles (healthy and atretic) and very strong in all secondary interstitial cells located in different regions of the ovary, but weak in TIC of preantral follicles. The IGFBP-3 hybridization signal was localized specifically to some corpora lutea. Here the hybridization single for IGFBP-3 was strong and distributed throughout the corpus luteum, strong but localized to only some luteal cells, or not detectable. The IGFBP-4 mRNA was localized almost exclusively to granulosa cells of atretic follicles. The intensity of the IGFBP-4 signals appeared to increase as the level of atresia increased. In some cases, IGFBP-4 signals were detected in the TIC, but they were weak and variable. These results show that the mRNAs for IGFBP-2, -3, and -4 are localized to the interstitial cells, corpora lutea, and atretic granulosa cells, respectively. The tissue-specific synthesis of IGFBP subtypes in specialized ovarian cells provides an excellent system to study the manner in which IGFBP synthesis is controlled and their potential role as an autocrine and paracrine factors.