COMPARATIVE IL-6 EFFECTS ON FSH-INDUCED AND HCG-INDUCED FUNCTIONS IN PORCINE GRANULOSA-CELL CULTURES

Gonadotropin regulation of granulosa cell (GC) differentiation can be modulated by nonsteroidal factors, including cytokines. Interleukin-6 (IL-6), a broad spectrum cytokine, has been previously demonstrated to be produced by GCs and to directly influence follicle stimulating hor mone (FSH) differentiated functions of ovarian GCs. In the present stu dy, primary cultures of GCs were prepared from prepubertal sow ovaries . No significiant amount of biological active IL-6 was detected in the se cultures using the B9 cell growth bioassay. Although our findings s uggest that GCs are not source of IL-6 in the porcine ovary, this cyto kine may be released by leukocytes present in the ovary and modulate o varian functions by acting on GCs. Here, adding recombinant human (rh) IL-6 to GC cultures inhibited differentiated functions induced by FSH such as aromatase activity, LH receptor (LHr) expression measured by s pecific I-125-hCG binding and progesterone (P) production. On the oppo site, rhIL-6 did not modulate stimulatory human chorionic hormone (hCG ) effects on P release by GCs and did not prevent hCG binding to LHr. These preliminary results clearly showed that IL-6 acted differently o n FSH and hCG induced functions although these gonadotropins act prima rily through the same transduction pathway involving generation of cyc lic AMP. We suggest that IL-6 might act more likely by reducing FSH bi nding capacity than by modulating transduction pathways. Inhibitory IL -6 effects on FSH-induced functions were not neutralized by adding to culture media a monoclonal antibody against the human IL-6 signal tran sducer gp130, previously reported to inhibit IL-6 mediated effects in human cell lines.