促性腺激素释放激素激动剂对子宫肌瘤细胞泌乳素生成的作用

目的研究促性腺激素释放激素激动剂(GnRHa)对体外培养的子宫肌瘤细胞泌乳素生成的抑制作用.方法来源于行子宫切除术的绝经前妇女的肌瘤细胞进行原代培养,10%胎牛血清或双丁酰环磷腺苷(db-cAMP)作用24,48,72,96 h后测定上清液中泌乳素(PRL)的浓度.再在上述培养液中加入GnRHa(buserelin 10-5M)后,同样的时段测定PRL浓度.采用半定量反转录PCR法测定GnRHa作用后的GnRH受体mRNA表达的变化.结果胎牛血清和db-cAMP可刺激PRL的产生,db-cAMP的刺激作用更强,并且PRL量随db-cAMP作用时间和剂量的增加而增加.在作用96 hGnRHa对对照组(不含胎牛血清)和10%胎牛血清组PRL产生有明显抑制,但db-cAMP对PRL的刺激作用不会被GnRHa所抑制.GnRHa在48 h对GnRH受体mRNA表达有轻微下调.结论GnRHa对子宫肌瘤细胞PRL的产生有直接抑制作用.由于GnRHa无法抑制db-cAMP对PRL的刺激作用,其抑制作用位点可能位于蛋白激酶A途径环磷酸腺苷位点以上.

Effect of gonadotropin-releasing hormone agonist on prolactin production by human leiomyoma cells

Objective: To assess the inhibitory effect of gonadotropin-releasing hormone agonist (GnRHa) on the prolactin (PRL) production by human leiomyoma cells in vitro.Methods:Primary monolayer cultures of leiomyoma were established using tissues from ten premenopausal women undergoing hysterectomy. PRL concentration was measured at 24,48,72 and 96 hours after the treatment with 10% fetal bovine serum(FBS) or dibutyryl cyclic adenosine monophosphate(db-cAMP). Leiomyoma cells, which were stimulated by 10% FBS or db-cAMP, were treated with 10 -5 M GnRHa(buserelin)and PRL concentration was measured in the same time course. The expression of GnRH receptor mRNA after the treatment of GnRHa on human leiomyoma cells was analyzed by semiquantitative RT-PCR .Results: PRL production was stimulated by FBS and db-cAMP, especially db-cAMP strongly stimulated PRL production in a time and dose-dependentmanner. GnRHa inhibited PRL production in both control(FBS-free) and 10% FBS groups at 96 hours significantly. However, GnRHa did notinhibitPRLproductionstimulatedbydb-cAMP . The expression of GnRH receptor mRNA was slightly down-regulated by GnRHa at 48 hour.Conclusion: It is suggested that GnRHa might have a direct inhibitory effect on PRL production by leiomyoma cells. Since GnRHa did not inhibit PRL production stimulated by db-cAMP, its action point might be located up-stream of cAMP in protein kinase A (PKA) cascade.