Oxytocin-induced cell growth proliferation in human myometrial cells and leiomyomas

Abstract

To assess the expression of the oxytocin receptor (OTR) and the role of oxytocin (OT) in the proliferation of myometrial and leiomyoma cells. Prospective laboratory study. Research laboratory at the Italian National Research Council. Twenty-two women who underwent therapeutic myomectomy for fibroids. Primary cultures of leiomyoma and myometrium cells were established from eutopic and ectopic myometrial tissues. An immortalized myometrial cell line (h-TERTmyo) and a leiomyosarcoma cell line (SK-UT-1) were also characterized. Expression of OTR and desmin mRNA was determined by quantitative real-time polymerase chain reaction. Cell growth was determined by 3-[4,5-dimethylthiazol-2-yl]5-(3-carboxymethoxyphenyl)2-(4-sulfophenyl)-2H tetrazolium assay. Apoptosis was determined by annexin V cell staining and flow cytometry analysis. Oxytocin stimulated proliferation of primary myometrial and leiomyoma cells but inhibited the proliferation of h-TERTmyo and SK-UT-1, indicating a change in phenotype during immortalization. A progressive and rapid decrease in desmin and OTR mRNA was observed in primary cultures, indicating that myometrial cells dedifferentiate very rapidly in culture. The relative expression of OTR mRNA varied widely in both myometrial and leiomyoma smooth muscle cells, but there was no significant difference. These results indicate that OT stimulates the proliferation of both myometrial and leiomyoma cells, demonstrating that the OT/OTR system plays an important role in regulating uterine cell growth and providing a rationale for evaluating the use of OTR antagonists in managing uterine myomas.