Urocortin stimulates placental adrenocorticotropin and prostaglandin release and myometrial contractility in vitro.
Urocortin is a new member of the CRF family. Multiple biological effects for urocortin have been shown in rats and in some in vitro models, showing a modulatory role in hormonal and behavioral functions. Human placenta expresses urocortin, but no information is available on the possible local biological actions. The aim of the present study was to evaluate the effect of urocortin on placental ACTH and prostaglandin (PG) secretion, as well as on myometrial contractility. Various in vitro models were used. For investigating the effect of urocortin on ACTH release, primary cultures of human trophoblast cells were used. Culture 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 prostaglandin E2 (PGE2) levels were measured by RIA. Strips of myometrial tissue were incubated in an organ bath and connected to an isometric smooth-muscle transducer in the presence of urocortin, with or without prostaglandin F2alpha (PGF2a). 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 urocortin, whereas astressin inhibited urocortin-stimulated ACTH or PGE2 release. Equimolar doses of CRF showed a similar effect on both ACTH and PGE2. Urocortin increased PGF2alpha-induced myometrial contractility, and this effect was completely abolished by the addition of astressin. The present study showed that human urocortin stimulates placental secretion of ACTH and PGE2, and modulates myometrial contractility, suggesting a role for this peptide in placental and intrauterine CRF pathways.
Petraglia
F
F
Department of Surgical Sciences, University of Udine, Italy. felice.petraglia@dsc.uniud.it
Florio
P
P
Benedetto
C
C
Marozio
L
L
Di Blasio
A M
AM
Ticconi
C
C
Piccione
E
E
Luisi
S
S
Genazzani
A R
AR
Vale
W
W
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D054832:Urocortins; D014590:Uterine Contraction / Q000187:drug effects*
D054832:Urocortins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D015237:Dinoprost; D015232:Dinoprostone