Dibbs K I, Anteby E, Mallon M A, Sadovsky Y, Adler S
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Biol Reprod. 1997 Dec;57(6):1285-92. doi: 10.1095/biolreprod57.6.1285.
The mechanism of labor initiation in humans has not been completely elucidated. Prostaglandins, estrogens, and corticotropin-releasing factor (CRF) have all been shown to affect uterine myocytes and enhance uterine contractility. There are also indications that these uterine regulators have additional effects on other sites involved in labor and that they may act in concert or, perhaps, by regulating each other. Therefore, we evaluated the CRF promoter for transcriptional regulation by prostaglandins and estrogens. Human placental choriocarcinoma cell lines were transfected with CRF-luciferase reporter genes and treated with prostaglandins. Prostaglandin E2 (PGE2), but not prostaglandin F2alpha (PGF2alpha), stimulated CRF-luciferase expression in choriocarcinoma cell lines via a cAMP-dependent pathway. A combination of transfections and in vitro binding studies tested for potential regulation of CRF by estrogen receptor (ER). ER neither regulated the CRF promoter nor interacted with steroid response half-sites from the CRF promoter. Our results provide a molecular regulatory link between PGE2 and CRF, two compounds that enhance uterine contractile function. Combined with the stimulation of prostaglandin release by CRF, these data support a potentially important "feed-forward" regulatory loop involving CRF and PGE2 in parturition. In contrast, we found no evidence for direct effects of estrogens or PGF2alpha on CRF transcription.
人类分娩发动的机制尚未完全阐明。前列腺素、雌激素和促肾上腺皮质激素释放因子（CRF）均已被证明可影响子宫肌细胞并增强子宫收缩力。也有迹象表明，这些子宫调节因子对参与分娩的其他部位有额外作用，且它们可能协同作用，或者可能通过相互调节发挥作用。因此，我们评估了前列腺素和雌激素对CRF启动子的转录调控作用。用人胎盘绒毛膜癌细胞系转染CRF - 荧光素酶报告基因并用前列腺素处理。前列腺素E2（PGE2）而非前列腺素F2α（PGF2α）通过cAMP依赖性途径刺激绒毛膜癌细胞系中CRF - 荧光素酶的表达。通过转染和体外结合研究相结合的方法检测雌激素受体（ER）对CRF的潜在调控作用。ER既不调节CRF启动子，也不与CRF启动子的类固醇反应半位点相互作用。我们的结果提供了PGE2和CRF之间的分子调控联系，这两种化合物均可增强子宫收缩功能。结合CRF对前列腺素释放的刺激作用，这些数据支持了分娩过程中涉及CRF和PGE2的一个潜在重要的“前馈”调节环路。相比之下，我们没有发现雌激素或PGF2α对CRF转录有直接影响的证据。
