Comparison of immunocytologic localization of insulin-like growth factor binding protein-4 in normal and polycystic ovary syndrome human ovaries.

Abstract

The cytologic localization and cellular levels of insulin-like growth factor binding protein-4 (IGFBP-4) in follicular and stromal compartments of normal and polycystic ovary syndrome (PCOS) ovaries during follicular growth and regression were investigated by the avidin/biotin immunoperoxidase method with a polyclonal antibody to human IGFBP-4, and a comparative assessment of IGFBP-4 expression in normal and PCOS ovaries was provided. In normal human ovaries, IGFBP-4 was immunolocalized to the oocyte throughout follicular growth, while the surrounding granulosa and theca cells were negligible for IGFBP-4 immunostaining in primordial, preantral and antral follicles. IGFBP-4 immunostaining became apparent, however, in the lutein cells of corpora lutea and the granulosa and theca cells of atretic follicles. In PCOS ovaries, prominent immunostaining for IGFBP-4 was apparent not only in the oocyte, but also in the surrounding granulosa cells in preantral follicles. In antral follicles from PCOS women without hyperinsulinemia, IGFBP-4 immunostaining was more prominent in the granulosa cells than the theca cells, 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 of the association of hyperinsulinemia. These results demonstrate for the 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 IGF-1, the abundant expression of IGFBP-4 in granulosa and theca cells of preantral and antral follicles of PCOS ovaries may lead to decreases in the bioavailability of IGF-I in those follicles. The decrease in IGF-I-mediated stimulation of gonadotropin actions 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.