Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta.
The levels of immunoreactive CRH are elevated in both maternal and fetal plasma in late gestation and labor, but fall precipitously after parturition. The major source of this peptide is thought to be the placenta. We determined if the placenta and also the amnion, chorion, and decidua produce CRH, whether this material has biological activity, and whether CRH output is modulated by glucocorticoids and progesterone. In an in vitro monolayer culture system CRH was produced by the fetal membranes and decidua. Media immunoreactive CRH concentrations averaged 625 +/- 45 (SE) pg/10(5) cells in amnion, 701 +/- 56 pg/10(5) cells in chorion, and 580 +/- 60 pg/10(5) cells in decidual tissue obtained at cesarean section. This output was similar to that by the placenta (906 +/- 121 pg/10(5) cells). These values increased in tissue obtained after spontaneous labor. A single peak of CRH immunoreactivity eluting at the same position as synthetic human CRH, and possessing biological activity, was found in all tissues. There was a dose-dependent increase in CRH output by all tissue types when cells were maintained in the presence of increasing concentrations of cortisol and dexamethasone. In contrast, increasing concentrations of progesterone decreased CRH output by all tissue types. We conclude that immuno- and biologically active CRH is produced not only in the human placenta, but also in the fetal membranes. CRH output by the placenta/fetal membranes is moderated by steroids, and changes with labor. These findings raise the possibility of a regulatory system similar to that of the hypothalamic pituitary axis, but residing within the placenta and fetal membranes.
Jones
S A
SA
Lawson Research Institute, St. Joseph's Health Centre, Department of Obstetrics and Gynaecology, London, Ontario, Canada.
Brooks
A N
AN
Challis
J R
JR
D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000328:Adult; D002850:Chromatography, Gel; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D003470:Culture Media / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007743:Labor, Obstetric; D009924:Organ Culture Techniques; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011863:Radioimmunoassay
D003470:Culture Media; D005938:Glucocorticoids; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone