Oxygen regulation of placental 11β-hydroxysteroid dehydrogenase 2: Physiological and pathological implications

N. Alfaidy, S. Gupta, C. DeMarco, I. Caniggia, J. R G Challis

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    Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The genesis of PE is related to deficient trophoblast invasion of maternal spiral arteries, which might result in a reduction of placental (PL) oxygen (O 2). An absence of increased O 2 that normally occurs around the 10-12th wk of gestation results in aberrant expression of genes that might contribute to the pathophysiology of PE. We examined the expression and regulation of PL 11β-hydroxysteroid dehydrogenase 2 (11β-HSD) in normal pregnancies and in PE. Two types of 11β-HSD exist in the placenta, 11β-HSD1 and 11β-HSD2. 11β-HSD2 is thought to protect the fetus from cortisol excess. In PE, both the expression and activity of PL 11β-HSD2 were reduced significantly compared with those in age-matched controls. As PE is associated with a reduction of PL O 2, we next investigated whether in normal pregnancy 11β-HSD2 expression changes at the time of the increase in O 2. 11β-HSD2 was detected as early as 5 wk, with expression limited to the syncytiotrophoblast (ST). At 10-12 wk, this expression increased and was also found in the cytotrophoblast and extravillous trophoblast. These results were substantiated by Western blot. The ability of O 2 to regulate 11β-HSD2 was determined both in cultures of villous explant from early gestation and in term trophoblast cells after incubation under 3% or 20% O 2. Villous explants cultured under 20% O 2 showed higher enzyme activity and expression compared with 3% O 2. Term trophoblast cells also exhibited higher enzyme activity at 20% vs. 3% O 2. No change in 11βHSD1 expression was observed in early pregnancy or in PE. This is the first report to suggest that 11β-HSD2 is O 2 dependent in first and third trimester placenta during human gestation.
    Original languageEnglish
    Pages (from-to)4797-4805
    Number of pages8
    JournalJournal of Clinical Endocrinology and Metabolism
    Issue number10
    Publication statusPublished - 1 Oct 2002


    • 11-beta-Hydroxysteroid Dehydrogenase Type 2
    • Blotting, Western
    • Cells, Cultured
    • Female
    • Gestational Age
    • Humans
    • analysis: Hydroxysteroid Dehydrogenases
    • Immunohistochemistry
    • administration & dosage: Oxygen
    • enzymology: Placenta
    • enzymology: Pre-Eclampsia
    • Pregnancy
    • Research Support, Non-U.S. Gov't
    • Tissue Distribution
    • enzymology: Trophoblasts


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