Urocortin stimulates placental adrenocorticotropin and prostaglandin release and myometrial contractility in vitro

Urocortin is a new member of the CRF family. Multiple biological effects fo r urocortin have been shown in rats and in some in vitro models, showing a modulatory role in hormonal and behavioral functions. Human placenta expres ses urocortin, but no information is available on the possible local biolog ical actions. The aim of the present study was to evaluate the effect of ur ocortin on placental ACTH and prostaglandin (PG) secretion, as well as on m yometrial contractility. Various in vitro models were used. For investigating the effect of urocorti n on ACTH release, primary cultures of human trophoblast cells were used. C ulture media, collected before and after 3 h exposure to different doses of urocortin and ACTH, were measured by RIA. Trophoblast tissue explants were incubated for 24 h in the presence of increasing doses of urocortin, and p rostaglandin E2 (PGE2) levels were measured by RIA. Strips of myometrial ti ssue were incubated in an organ bath and connected to an isometric smooth-m uscle transducer in the presence of urocortin, with or without prostaglandi n F2 alpha (PGF2 alpha). In all these experiments, the effect of astressin (a CRF receptor antagonist) on urocortin-induced actions and the effect of equimolar doses of CRF were evaluated. A dose-related increase of trophoblast ACTH or PGE2 was induced by urorcort in, whereas astressin inhibited urocortin-stimulated ACTH or PGE2 release. Equimolar doses of CRF showed a similar effect on both ACTH and PGE2. Uroco rtin increased PGF2 alpha-induced myometrial contractility, and this effect was completely abolished by the addition of astressin. The present study showed that human urocortin stimulates pla cental secreti on of ACTH and PGE2, and modulates myometrial contractility, suggesting a r ole for this peptide in placental and intrauterine CRF pathways.