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.

Uterine rupture, a potentially catastrophic complication during pregnancy, has been reported to occur spontaneously in the second and third trimesters. We describe a case of spontaneous uterine rupture at 8 weeks' gestation in a 29-year-old woman, who has a history of systemic lupus erythematosus. The diagnosis was established with the aid of ultrasound imaging. She underwent local excision of the perforated area of the uterus. Histologic examination revealed exuberant intermediate trophoblast. On follow-up, human chorionic gonadotropin (hCG) titers returned to normal over a 15-week period. We conclude that spontaneous uterine rupture can occur in the first trimester, and early utilization of ultrasound could help in the management of this serious condition.

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