Anderson Laurie, Martin William, Higgins Claire, Nelson Scott M, Norman Jane E
Reproductive and Maternal Medicine, Institute of Biomedical and Life Sciences University of Glasgow, Scotland, UK.
Reprod Sci. 2009 Nov;16(11):1052-61. doi: 10.1177/1933719109340926. Epub 2009 Jul 14.
Recent clinical trials have demonstrated a beneficial effect of supplementation with progesterone to prevent preterm labor. We aimed to determine the effects of progesterone treatment in vitro and in vivo and 17alpha-hydroxyprogesterone caproate (17OHPC) in vitro on myometrial contractions.
Myometrial strips were taken from women undergoing cesarean delivery at term. We also obtained myometrial biopsies from women participating in a clinical trial of progesterone to prevent preterm labor in twins (STOPPIT). After establishment of spontaneous contractions, strips were exposed to progesterone or 17OHPC. Separate strips were exposed to oxytocin and tocolytics alone and in combination with progesterone. Potassium channel blockers were added in conjunction with progesterone. STOPPIT samples were used to compare the effects of in vivo progesterone and placebo. We measured amplitude, frequency and activity integral of contractions.
Maximum inhibition of contraction amplitude was 93 +/- 2% and 67 +/- 14% for progesterone at 30 microM and vehicle (70% ethanol), respectively, P < 0.05. 17OHPC did not exert an inhibitory effect. Water soluble progesterone exerted a maximal inhibitory effect on amplitude of contractions of 82 +/- 10% at 100 microM, P < 0.05. The inhibitory effect of progesterone was unaffected by potassium channel blockers. There was no difference between in vivo placebo and progesterone-treated groups in either amplitude or frequency of contractions, nor was there any difference in the response to oxytocin or the tocolytic drugs.
Progesterone exerts rapid inhibition of the amplitude of myometrial contractions in vitro but 17OHPC does not. The action of progesterone does not appear to operate via potassium channels nor does it enhance the activity of certain tocolytic drugs.
近期的临床试验已证明补充孕酮对预防早产有有益作用。我们旨在确定孕酮在体外和体内的作用以及己酸羟孕酮(17OHPC)在体外对子宫肌层收缩的影响。
从足月行剖宫产的女性身上获取子宫肌层条带。我们还从参与孕酮预防双胎早产临床试验(STOPPIT)的女性身上获取子宫肌层活检组织。在建立自发收缩后,将条带暴露于孕酮或17OHPC。将单独的条带分别暴露于催产素和宫缩抑制剂,以及与孕酮联合使用。在使用孕酮的同时添加钾通道阻滞剂。使用STOPPIT样本比较体内孕酮和安慰剂的效果。我们测量了收缩的幅度、频率和活动积分。
孕酮在30微摩尔时对收缩幅度的最大抑制率为93±2%,而在溶媒(70%乙醇)中为67±14%,P<0.05。17OHPC未发挥抑制作用。水溶性孕酮在100微摩尔时对收缩幅度的最大抑制率为82±10%,P<0.05。孕酮的抑制作用不受钾通道阻滞剂的影响。体内安慰剂组和孕酮治疗组在收缩幅度或频率上均无差异,对催产素或宫缩抑制剂的反应也无差异。
孕酮在体外能迅速抑制子宫肌层收缩的幅度,但17OHPC不能。孕酮的作用似乎不是通过钾通道发挥的,也不会增强某些宫缩抑制剂的活性。