Hepatocyte Growth Factor and Stem Cell Factor Involvement in Paracrine Interplays of Theca and Granulosa Cells in the Human Ovary

Objective: To examine gene expression of hepatocyte growth factor (HGF), the receptor for HGF, c-met, and the receptor for stem cell factor (SCF), c-kit, in the human ovary and to investigate the effects of HGF and SCF on the proliferation and function of granulosa and theca cells.

Design: Prospective study.

Setting: University hospital.

Patient(s): Six premenopausal women.

Intervention(s): Follicular fluid and granulosa cells were collected during IVF cycles. Ovarian tissues were obtained from women who underwent surgery.

Main Outcome Measure(s): Gene expression of HGF, c-met, and c-kit in the human ovary was determined.

Result(s): Reverse-transcription polymerase chain reaction showed the presence of HGF and c-kit mRNA in the theca and stroma cells of the ovary, whereas c-met mRNA was observed in the granulosa, theca, and stroma cells. HGF increased the expression of SCF gene in granulosa cells, and SCF reciprocally increased the expression of HGF gene in theca cells. SCF stimulated the proliferation of theca cells. HGF stimulated progesterone production in granulosa cells.

Conclusion(s): A positive feedback loop between theca cells and granulosa cells was identified that is mediated by HGF and SCF. HGF and SCF modulate the interplay between theca and granulosa cells by promoting cell proliferation and steroid hormone production.