Influence of tumor necrosis factor-alpha on estradiol, progesterone, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, 2, and 3 in cultured human luteinized granulosa cells

Abstract

Objective: The objective was to investigate the influence of tumor necrosis factor (TNF)-alpha on estradiol, progesterone, insulin-like growth factor (IGF)-II, and insulin-like growth factor binding protein (IGFBP)-1, 2, and 3 in cultured human luteinized granulosa cells.

Study design: Human luteinized granulosa cells were obtained from follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). The cells were cultured for 72 h with TNF-alpha at concentrations of 1.0, 10.0, and 100.0 ng/ml. The cells not treated with TNF-alpha served as controls. Radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to examine the influence of TNF-alpha on estradiol, progesterone, IGF-II, and IGFBP-1, 2, and 3. Results were analyzed using the Kolmogorov-Smirnov test and analysis of variance (ANOVA). Statistical significance was defined as p<0.05.

Results: The concentrations of progesterone seemed to decrease as the concentrations of TNF-alpha increased and the concentration of progesterone in the 100.0 ng/ml TNF-alpha group was significantly lower than that in the control and other TNF-alpha groups. The expressions of IGF-II mRNA in the 10.0 and 100.0 ng/ml TNF-alpha groups were significantly lower than that in the control group. The expressions of IGFBP-2 mRNA seemed to be decreased in the 10.0 and 100.0 ng/ml TNF-alpha groups compared with that in the control group, but there were no statistical significances.

Conclusion: TNF-alpha may play a role as a regulator of human ovarian physiology by modulating the IGF systems in luteinized granulosa cells.