Astle Shirley, Khan Raheela N, Thornton Steven
Department of Biological Sciences, University of Warwick, Coventry, UK.
BJOG. 2003 Jun;110(6):589-92. doi: 10.1046/j.1471-0528.2003.02041.x.
To determine the effect of the progesterone metabolite 5 beta-dihydroprogesterone on human oxytocin receptor binding in myometrial membranes and on whole-cell calcium current in single myometrial cells.
Receptor binding studies in human myometrial membranes prepared from biopsies taken before or after the onset of labour and in Chinese hamster ovary cells expressing the human oxytocin receptor. Whole cell patch-clamp experiments were undertaken on isolated myometrial cells.
University research laboratories and University hospital.Patients undergoing caesarean section at term either prior to or following onset of labour.
Myometrial biopsies were taken from women undergoing caesarean section. The binding affinities of oxytocin, 5 beta-dihydroprogesterone and atosiban were determined in myometrial membranes and Chinese hamster ovary cells expressing the human oxytocin receptor. The effect of 5 beta-dihydroprogesterone on inward current was also determined in isolated myometrial cells. Receptor binding affinity and electrophysiological inward current.
5 beta-Dihydroprogesterone did not reduce oxytocin receptor binding in myometrial membranes or Chinese hamster ovary cells expressing the human oxytocin receptor. Nor did it influence calcium current under whole-cell patch conditions in single myometrial cells. In contrast, atosiban inhibited binding in myometrial membranes prepared from samples taken either prior to or following labour (K(i) = 112 and 108 nM, respectively). The affinity of atosiban for the oxytocin receptor was much lower than oxytocin (K(i) = 5 and 6 nM in samples taken before or after labour, respectively) in myometrial membranes and in Chinese hamster ovary cells expressing the human oxytocin receptor (K(i) = 63 M and 1 nM for atosiban and oxytocin, respectively).
We conclude that 5 beta-dihydroprogesterone is unlikely to regulate myometrial activity as a result of a direct effect on oxytocin receptor binding or inward calcium current.
确定孕酮代谢产物5β-二氢孕酮对人子宫肌层膜中催产素受体结合以及单个子宫肌层细胞全细胞钙电流的影响。
对分娩开始前或分娩后获取的活检组织制备的人子宫肌层膜以及表达人催产素受体的中国仓鼠卵巢细胞进行受体结合研究。对分离的子宫肌层细胞进行全细胞膜片钳实验。
大学研究实验室和大学医院。足月行剖宫产的产妇，分娩开始前或开始后。
从行剖宫产的女性获取子宫肌层活检组织。测定催产素、5β-二氢孕酮和阿托西班在子宫肌层膜以及表达人催产素受体的中国仓鼠卵巢细胞中的结合亲和力。还在分离的子宫肌层细胞中测定5β-二氢孕酮对内向电流的影响。受体结合亲和力和电生理内向电流。
5β-二氢孕酮未降低子宫肌层膜或表达人催产素受体的中国仓鼠卵巢细胞中的催产素受体结合。在单个子宫肌层细胞的全细胞膜片钳条件下，它也不影响钙电流。相比之下，阿托西班抑制分娩前或分娩后获取样本制备的子宫肌层膜中的结合（抑制常数分别为112和108 nM）。在子宫肌层膜以及表达人催产素受体的中国仓鼠卵巢细胞中，阿托西班对催产素受体的亲和力远低于催产素（分娩前或分娩后样本中催产素的抑制常数分别为5和6 nM）（阿托西班和催产素的抑制常数分别为63 nM和1 nM）。
我们得出结论，5β-二氢孕酮不太可能因对催产素受体结合或内向钙电流的直接作用而调节子宫肌层活性。
