title: Late gestation increase in 11beta-hydroxysteroid dehydrogenase 1 expression in human fetal membranes: a novel intrauterine source of cortisol.
abstract: Late human gestation is associated with an increase in the concentration of cortisol (F) in the fetal circulation and amniotic fluid. It had been assumed that most of the F measured in the amniotic fluid came from the fetal adrenal gland. However, local production of F can also occur in human intrauterine tissues from inactive cortisone under the influence of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1. Recent studies have shown that 11beta-HSD 1 activity is up-regulated by prostaglandins (PG) E2 and F2alpha, hormones that are produced in the fetal membranes (FM) at term. In the present study, we hypothesized that 11beta-HSD 1 expression would increase in FM during pregnancy and at labor, creating the potential for local increase in F production at term. We examined 11beta-HSD 1 expression in placenta and FM obtained during normal pregnancy from nonlaboring women [26-28 wk (n = 3); 29-30 wk (n = 3); 32-33 wk (n = 3); 35-36 wk (n = 3)] and from uncomplicated term pregnancies after elective cesarean section (n = 6). 11beta-HSD 1 expression was also examined in amnion and chorionic tissues in relation to term labor (n = 12). Immunohistochemistry and Western blot analysis were used to examine 11beta-HSD 1 localization and expression. 11beta-HSD 1 activity was also measured in microsomal fractions prepared from whole fetal membranes. At term, immunoreactive 11beta-HSD 1 expression was localized predominantly to the chorion trophoblast cells, attached decidua, and amnion epithelial cells. 11beta-HSD 1 expression in FM increased with gestational age and reflected increased enzyme reductase activity. No change in 11beta-HSD 1 expression was found in placental tissue from the same patients. There was a significant increase in 11beta-HSD 1 expression in amnion but not in chorion with the onset of labor. We suggest that increases in 11beta-HSD 1 expression/activity by intrauterine membranes during late gestation may result in increased potential for a local increase in F production and that FM should be considered as an extraadrenal source of F during late gestation. This local F production may be involved in different pathways contributing to the regulation of parturition.
authors.affiliation: Canadian Institutes for Health Research (CIHR), Institute of Human Development, Child and Youth Health, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. n.alfaidy@utoronto.ca
authors.forename: Nadia
authors.initials: N
authors.lastname: Alfaidy
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Tracy
authors.initials: T
authors.lastname: MacIntosh
authors.forename: Kaiping
authors.initials: K
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Challis
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000650:Amnion / Q000201:enzymology*; D002823:Chorion / Q000201:enzymology*; D005260:Female; D005333:Fetus / Q000201:enzymology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007743:Labor, Obstetric / Q000502:physiology; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third
chemical_list: D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D006854:Hydrocortisone