Placental 11 beta-hydroxysteroid dehydrogenase: barrier to maternal glucocorticoids.
During mammalian pregnancy, the circulating concentration of cortisol (in rodents, corticosterone) in the mother is much higher than that in the fetus. Since the placenta is the only barrier, apart from the uterus, between the mother and her fetus, this gradient in cortisol concentrations suggests that there is a placental barrier preventing maternal cortisol from crossing into the fetus. The intracellular enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is an ideal candidate for this barrier because it interconverts cortisol and corticosterone to their inactive metabolites cortisone and 11-dehydrocorticosterone. Indeed, 11 beta-HSD enzyme is expressed in the placenta of humans and a range of other animal species. Moreover, it is well positioned to serve as the barrier since it is localized to the syncytiotrophoblast, the site of maternal-fetal exchange. Given that fetal exposure to excessive amounts of glucocorticoids leads to intrauterine growth retardation, it has been hypothesized that the physiological significance of this placental 11 beta-HSD barrier is to protect the fetus from adverse effects of maternal glucocorticoids.
Yang
K
K
Lawson Research Institute, St. Joseph's Health Centre, Department of Obstetrics/Gynecology, University of Western Ontario, London, Canada.
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001692:Biological Transport; D003345:Corticosterone / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013045:Species Specificity
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone; D006854:Hydrocortisone