Insulin-like growth factor-binding proteins in healthy and atretic follicles during natural menstrual cycles.

An increasing body of evidence suggests a regulatory role for insulin-like growth factor-binding proteins (IGFBPs) in ovarian folliculogenesis. Although IGFBPs have been identified in the follicular fluid (FF) from women undergoing hyperstimulation for in vitro fertilization, little is known about the pattern of IGFBP expression during follicle development in natural menstrual cycles. The purpose of the present study was to determine the pattern of IGFBPs in the FF of healthy and atretic follicles during the follicular phase of natural menstrual cycles. FF was aspirated from follicles in normal ovaries of regularly cycling women. Dominant follicles were identified as the largest follicle in either ovary with an androstenedione to estradiol ratio in the FF of 4 or less. The androstenedione/estradiol ratio in atretic follicles was greater than 4. IGFBPs in the FF samples were analyzed by ligand blotting with [125I]IGF-II. The identities of the BPs measured by ligand blotting were confirmed by immunoblot and RIA analysis. IGFBP-3 concentrations decreased in healthy follicles as the follicular phase progressed. IGFBP-3 levels were significantly lower in dominant than healthy cohort follicles. IGFBP-2 was elevated in atretic follicles relative to that in healthy follicles. The levels of a 29-kilodalton BP comigrating with IGFBP-1 did not change significantly. IGFBP-4 was detected in only some of the atretic follicles. These experiments demonstrate that 1) at least four distinct IGFBPs are present in FF of women with natural unstimulated menstrual cycles; 2) IGFBP-3 in FF decreases during folliculogenesis, and 3) IGFBP-2 levels are elevated in atretic follicles. These data support the concept that IGFBPs may play important roles in regulating follicle selection and atresia.