Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by Progesterone, Estrogen, and the Cyclic Adenosine 5′-Monophosphate Pathway in Cultured Human Placental and Chorionic Trophoblasts1
Abstract
Human placenta and fetal membranes contain two types of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). 11Beta-HSD1 interconverts cortisol and cortisone and is the predominant isoform found in the fetal membranes. 11Beta-HSD2, which predominates in the placenta syncytiotrophoblast, converts cortisol to cortisone. It has been proposed that placental 11beta-HSD protects the fetus from high levels of maternal glucocorticoids. In this study, cultured term human placental and chorionic trophoblasts were used to examine the regulation of 11beta-HSD1 and 11beta-HSD2 activities and mRNA expression by progesterone, estrogen, and activators of adenylate cyclase (forskolin) and protein kinase C (phorbol 12-myristate 13-acetate, PMA). Placental trophoblast displayed mainly type 2 oxidase activities. 11Beta-HSD in the chorionic trophoblast was exclusively an 11beta-HSD1 reductase. Progesterone (0.001-1 microM) inhibited 11beta-HSD2 activity in a dose-dependent fashion. Inhibition of endogenous progesterone production with trilostane enhanced 11beta-HSD2 activity. The inhibitory effect of progesterone on 11beta-HSD2 activity was not reversed by the progesterone receptor antagonists RU-486 or onapristone. Progesterone (1 microM) also reduced levels of 11beta-HSD2 mRNA, an effect that was attenuated by both RU-486 and onapristone. Estradiol (1 microM) inhibited type 2 oxidase activity as well. Activation of adenylate cyclase by forskolin (100 microM) up-regulated both 11beta-HSD2 activity and mRNA expression; there was no effect of PMA (1 microM) on 11beta-HSD2. 11Beta-HSD1 reductase activity was unaffected by progesterone, estrogen, forskolin, or PMA in either the placental or chorionic trophoblasts. We conclude that both progesterone and estrogen are inhibitors of 11beta-HSD2 activity in term human placenta in vitro. Levels of 11beta-HSD2 activity and mRNA are increased by activation of the cAMP pathway. Progesterone also suppresses levels of 11beta-HSD2 mRNA.
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References 29 · Cited by 86
Research works printed but not linked: 6
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- Authors
- Sun, K., Yang, K., & Challis, J. R. G.
- Affiliations
- University of Toronto (CA)
- Western University (CA)
- Corresponding author
- Sun, Kang
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-06-01
- Volume
- 58
- Issue
- 6
- Pages
- 1379-1384
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2042256553
- Cited by
- 86
- References
- 29
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (University of Western Australia) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- 11β-hydroxysteroid dehydrogenase type 2, 11β-hydroxysteroid dehydrogenase type 1, placental trophoblast, chorionic trophoblast, progesterone, estradiol, cyclic AMP, protein kinase C, trilostane, antiprogestins, cortisone, glucocorticoid metabolism, gene expression regulation, enzyme regulation, RU486, onapristone
- MeSH terms
- Cyclic AMP, Cells, Cultured, Chorion, Estradiol, Female, Colforsin, Gene Expression Regulation, Humans, Hydroxysteroid Dehydrogenases, Placenta, Pregnancy, Progesterone, RNA, Messenger, Tetradecanoylphorbol Acetate, Trophoblasts, 11-beta-Hydroxysteroid Dehydrogenases
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