| The Effect of Interleukin-1 on The Production of Insulin-Like Growth Factors and Their Binding Proteins in Human Granulosa-Luteal Cells. |
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J Y Lee, E G Min, J K Kim, C S Suh, S H Kim, Y M Choi, S Y Moon |
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| Abstract |
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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. |
| Key Words:
Interleukin-1, Interleukin-1 receptor antagonist, IGFBPs, Granulosa-luetal cells |
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