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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 2 4,48,72 ,96h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 - 5 M )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 96hGnRHa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 48h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。
Objective To study the inhibitory effect of gonadotropin-releasing hormone agonist (GnRHa) on prolactin production in uterine fibroids. Methods The fibroblasts of premenopausal women who underwent hysterectomy were cultured in primary culture. The effect of 10% fetal bovine serum or db-cAMP 2, 4, 48, 72, Prolactin (PRL) concentration. After adding GnRHa (buserelin 10 - 5 M) to the above culture medium, the PRL concentration was measured in the same period. The changes of GnRH receptor mRNA expression after GnRHa treatment were determined by semi-quantitative reverse transcription PCR. Results Fetal bovine serum and db-cAMP stimulated the production of PRL, the stimulating effect of db-cAMP was stronger, and the amount of PRL increased with the time and dose of db-cAMP. The effect of 96hGnRHa on PRL production in the control group (without fetal bovine serum) and 10% fetal bovine serum was significantly inhibited, but the stimulating effect of db-cAMP on PRL was not inhibited by GnRHa. GnRHa slightly downregulates GnRH receptor mRNA expression at 48h. Conclusion GnRHa has a direct inhibitory effect on the production of PRL in uterine fibroids. Since GnRHa can not inhibit the stimulatory effect of db-cAMP on PRL, its inhibitory site may be located above the cAMP site of the protein kinase A pathway.