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

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.

Busnelli M ，Rimoldi V ，Viganò P ，Persani L ，Di Blasio AM ，Chini B ... -  《-》

Recombinant H2 relaxin inhibits apoptosis and induces cell proliferation in cultured leiomyoma cells without affecting those in cultured normal myometrial cells.

To evaluate the effects of human relaxin on proliferation and apoptosis in cultured human uterine leiomyoma cells and normal myometrial cells. In vitro experiment. Research laboratory at Kobe University Graduate School of Medicine. Nine patients undergoing hysterectomy for uterine leiomyoma. Cultured leiomyoma cells and normal myometrial cells were treated with human recombinant (rH2) relaxin. Human relaxin receptor LGR7 expressions in cultured leiomyoma cells and myometrial cells were evaluated by immunocytochemical staining. Cell proliferation, proliferating cell nuclear antigen-positive rate, and TUNEL-positive rate were assessed by MTS assay, immunocytochemistry, and TUNEL assay, respectively. Caspase-3 expression was evaluated by Western blot analysis. LGR7 expression was observed both in cultured human leiomyoma cells and myometrial cells. Compared with untreated control cultures, treatment with rH2 relaxin increased the number of viable cultured leiomyoma cells and the proliferating cell nuclear antigen-positive rate in those cells but not in myometrial cells. Moreover, treatment with rH2 relaxin decreased the TUNEL-positive rate in cultured leiomyoma cells but not in myometrial cells. Similarly, Western blot analysis revealed that treatment with rH2 relaxin decreased the expression of caspase-3 in cultured leiomyoma cells but not in myometrial cells. These results suggest that rH2 relaxin selectively inhibits apoptosis by down-regulating caspse-3 expression and induces proliferation in cultured human leiomyoma cells without affecting apoptosis or proliferation in normal myometrial cells.

Suzuki K ，Nakabayashi K ，Yamada AY ，Lodhi RS ，Hazama R ，Ebina Y ，Yamada H ... -  《-》

Comparative effects of SPRM asoprisnil (J867) on proliferation, apoptosis, and the expression of growth factors in cultured uterine leiomyoma cells and normal myometrial cells.

Ohara N ，Morikawa A ，Chen W ，Wang J ，DeManno DA ，Chwalisz K ，Maruo T ... -  《-》

Comparative effects of heparin-binding epidermal growth factor-like growth factor on the growth of cultured human uterine leiomyoma cells and myometrial cells.

Wang J ，Ohara N ，Takekida S ，Xu Q ，Maruo T ... -  《HUMAN REPRODUCTION》

Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling.

Cesen-Cummings K ，Houston KD ，Copland JA ，Moorman VJ ，Walker CL ，Davis BJ ... -  《-》