Korean J Obstet Gynecol.  1998 Jul;41(7):1795-1804.

The Effect of Interleukin-1 on The Production of Insulin-Like Growth Factors and Their Binding Proteins in Human Granulosa-Luteal Cells


The relationship between the immune system and the endocrine system in the ovary has become of an challenging and exciting subject to reproductive scientists. The intraovarian regulators such as insulin-like growth factor (IGF) system and interleukin-1 (IL-1) are believed to regulate ovarian function. This study was undertaken to investigate the effects of IL-1 on the production of IGFs and IGF binding proteins (IGFBPs) in human granulosa-luteal cells and to evaluate if this action is receptor mediated. The cells were recovered from follicular fluid obtained from women undergoing oocyte retrieval for in-vitro fertilization procedures. Purified granulosa-luteal cell preparations were cultured for 3 days in serum free media supplemented with IL-1, IL-1 receptor antagonist (IL-1ra), human chorionic gonadotropin (hCG) alone or these agents in combination. IGFs and IGFBPs in conditioned media were analyzed using double antibody radioimmunoassay, Western ligand blot and immunoprecipitation. No immunoreactive IGF-I was detectable in all conditioned media of granulosa luteal cells at a detectable level of 2 nM/L. At a concentration of 0.2-10 ng/ml both IL-1 and IL-1beta was found to stimulate IGF-II production. The accumulation of IGFBP-1, IGFBP-3 and IGFBP-4 in cultures of human granulosa-luteal cells was inhibited by both forms of IL-1 (0.2 ng/ml). Treatment of granulosa-luteal cell culture with hCG (0.1 g/ml) also resulted in a significant decrease in IGFBPs accumulation but concurrent treatment with IL-1beta (1 ng/ml) stimulated the accumulation of IGFBP-1 and IGFBP-4. IL-1ra (100 ng/ml) had no effect on the IGF production and IGFBPs accumulation when applied by itself but administration of an IL-1ra with IL-1beta (0.2 ng/ml) neutralized the IL-1beta-induced effect on the IGF production and IGFBPs accumulation in granulosa- luteal cells. These observations suggest that IL-1 modulate IGFBPs in human granulosa-luteal cell cultures and that this action of IL-1 is receptor-mediated.


Interleukin-1; Interleukin-1 receptor antagonist; IGFBPs; Granulosa-luetal cells
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