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Interaction of interleukin-6 on human granulosa cell steroid secretion
A Salmassi1, S Lü, J Hedderich
1Department of Obstetrics and Gynecology, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany. asalmassi@email.uni-kiel.de
Insights
Interleukin-6 (IL-6) inhibits estradiol and progesterone production by ovarian granulosa cells, potentially impacting female fertility during reproductive tract infections.
Area of Science:
- Reproductive Endocrinology
- Cell Biology
- Immunology
Background:
- Cytokines regulate ovarian function.
- Interleukin-6 (IL-6) is present in follicular fluid.
- Granulosa cells (GCs) are key to ovarian hormone production.
Purpose of the Study:
- To investigate the localization of IL-6 receptor and gp130 on GCs.
- To determine the effect of IL-6 on estradiol (E2) and progesterone (Prog) production by GCs in vitro.
- To explore IL-6's role in FSH-stimulated ovarian hormone release.
Main Methods:
- Immunocytochemistry to detect IL-6 receptor and gp130 on GCs.
- In vitro culture of GCs from infertile patients.
- Treatment of GCs with varying concentrations of IL-6 and FSH.
- Measurement of E2 and Prog in cell culture supernatants over time.
Main Results:
- IL-6 receptor and gp130 were localized on the surface of GCs.
- IL-6 significantly inhibited both basal and FSH-stimulated E2 production.
- IL-6 inhibited FSH-stimulated Prog release, but not basal release.
- Time-course studies confirmed IL-6's inhibitory effect on E2 and Prog secretion.
Conclusions:
- IL-6 plays a local regulatory role in FSH-stimulated E2 and Prog release.
- Elevated IL-6 levels during genital infections may contribute to reproductive dysfunction.
- IL-6's inhibitory effects on granulosa cells suggest a mechanism for infection-induced infertility.
Abstract:
Numerous studies have shown that a variety of cytokines are involved in the regulation of ovarian function. Interleukin-6 (IL-6), has been found in follicular fluid. In this report we show by immunocytochemical methods the localization of the extracellular domain of the IL-6-receptor and its associated signal transducer glycoprotein gp 130 on the surface of granulosa cells (GCs). The possibility that IL-6 may also influence the basal and FSH-stimulated production of estradiol (E2) and progesterone (Prog) by GCs in vitro was also investigated. GCs were obtained from infertile patients undergoing in vitro fertilization and embryo transfer treatment and cultured for 72 h or were given increasing concentrations of human recombinant IL-6 (8--128 pg/ml) in the absence or presence of FSH (96 U/ml). For the time-course studies, FSH-stimulated GCs were treated in the absence or presence of IL-6 (128 pg/ml) and supernatants were assayed at 24 h intervals (24-96 h) for E2 and Prog productions. The results show that increasing amounts of IL-6 significantly inhibit E2 production in the absence or presence of FSH vs untreated controls (P=0.025 at IL-6=128 pg/ml and P=0.016 at IL-6=16 pg/ml respectively). IL-6 also inhibited FSH-stimulated but not unstimulated Prog release (P=0.038 at IL-6=8 pg/ml). These findings suggest that IL-6 may be one of the factors that plays a local regulatory role in the course of FSH-stimulated E2 and Prog release. The time-course studies of the effect of the absence or presence of IL-6 demonstrated a significant inhibitory effect on both E2 and Prog secretion (P<0.001) by FSH-stimulated GCs. As infections of the female reproductive tract are often accompanied by elevated local IL-6 levels, this factor may be one of the links leading to endocrine reproductive dysfunction during genital infections.