COMPARISON OF IMMUNOCYTOLOGIC LOCALIZATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-4 IN NORMAL AND POLYCYSTIC-OVARY-SYNDROME HUMAN OVARIES

The cytologic localization and cellular levels of insulin-like growth factor binding protein-4 (IGFBP-4) in follicular and stromal compartme nts of normal and polycystic ovary syndrome (PCOS) ovaries during foll icular growth and regression were investigated by the avidin/biotin im munoperoxidase method with a polyclonal antibody to human IGFBP-4, and a comparative assessment of IGFBP-4 expression in normal and PCOS ova ries was provided. In normal human ovaries, IGFBP-4 was immunolocalize d to the oocyte throughout follicular growth, while the surrounding gr anulosa and theca cells were negligible for IGFBP-4 immunostaining in primordial, preantral and antral follicles. IGFBP-4 immunostaining bec ame apparent, however, in the lutein cells of corpora lutea and the gr anulosa and theca cells of atretic follicles. In PCOS ovaries, promine nt immunostaining for IGFBP-4 was apparent not only in the oocyte, but also in the surrounding granulosa cells in preantral follicles. In an tral follicles from PCOS women without hyperinsulinemia, IGFBP-4 immun ostaining was more prominent in the granulosa cells than the theca cel ls, whereas in antral follicles from PCOS women with hyperinsulinemia IGFBP-4 immunostaining was more prominent in the theca cells than the granulosa cells. Furthermore, in atretic follicles within PCOS ovaries IGFBP-4 immunostaining was prominent in the theca cells, regardless o f the association of hyperinsulinemia. These results demonstrate for t he first time that there is a great difference in cellular expression of IGFBP-4 between normal and PCOS human ovaries. In light of the high affinity of IGFBP-4 for TGF-I, the abundant expression of IGFBP-4 in granulosa and theca cells of preantral and antral follicles of PCOS ov aries may lead to decreases in the bioavailability of IGF-I in those f ollicles. The decrease in IGF-I-mediated stimulation of gonadotropin a ctions on granulosa and theca cells in preantral and antral follicles may impair the induction of aromatase activity, causing an androgenic microenvironment which is characteristic of atretic follicles and PCOS follicles.