Interaction of interleukin-6 on human granulosa cell steroid secretion

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 FSHstimulated 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.

Changes in Expression of Interleukin-6 Receptors in Granulosa Cells During Follicular Atresia in Pig Ovaries

“…In the present study, we investigated the changes in the expression of IL-6 receptors (IL-6Rα, IL-6sR and gp130) in granulosa cells and follicular fluid during atresia. The expressions of IL-6Rα and gp130 in human and rat granulosa cells [33,35] and IL-6sR in human follicular fluid [36] have previously been reported. We detected the expressions of IL-6Rα and gp130 in granulosa cells and IL-6sR in follicular fluid from the porcine ovary.…”

“…Recently, it has been revealed that many cytokines are involved in growth, differentiation, atresia, ovulation and luteinization in the ovary [27][28][29]. Although IL-6 affects the folliculogenesis and steroidgenesis of granulosa cells in the ovary [30][31][32][33], there is no clear information on the roles of IL-6 and its receptors in the regulation of granulosa cell apoptosis. As it has been reported that IL-6 and its receptors play important roles in the survival of various cells [17][18][19][20], we hypothesize that they are involved in follicular selection in the ovary.…”

IL-6 Promotes FSH-Induced VEGF Expression Through JAK/STAT3 Signaling Pathway in Bovine Granulosa Cells

“…Numerous studies have confirmed that inflammatory cytokines play an important regulatory role in ovarian activity [38-40]. In particular, the discovery and application of specific inhibitors and gene knockout animals have more substantiated the previous speculation about the involvement of inflammatory cytokines in follicular development and ovulation.…”

The Role of Interleukin-6 in the Regulation of Granulosa Cell Apoptosis During Follicular Atresia in Pig Ovaries

“…In the present study, we investigated whether or not IL-6 is involved in granulosa cell apoptosis during atresia. It has been reported that IL-6 is produced by granulosa cells in human, rat, and bovine ovaries and that it affects the folliculogenesis and steroidgenesis of granulosa cells [28][29][30][31], but in porcine ovaries, IL-6 is produced by immune cells such as macrophages and T cells, not granulusa cells [32]. In the present study, however, we confirmed that IL-6 mRNA was expressed in granulosa cells of healthy, early atretic, and progressed atretic follicles in porcine ovaries.…”