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Human placental 11 beta-hydroxysteroid dehydrogenase: evidence for and partial purification of a distinct NAD-dependent isoform.
Abstract
Excess glucocorticoids impair fetal growth and cause teratogenesis. Placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the inactivation of cortisol to cortisone, preventing the high maternal cortisol levels from reaching the fetal circulation and thus preserving the low cortisol fetal environment. In previous work, an NADP-dependent isoform of 11 beta HSD has been purified from rat liver, a cDNA isolated, and the human homolog cloned. However, much evidence suggests tissue-specific 11 beta HSD activities that cannot be explained by the liver-type isoform. Therefore, we have partially purified human placental 11 beta HSD and compared it to the enzyme in rat liver. Human placental subcellular fractions exhibited NAD-dependent 11 beta HSD activity, but showed little activity with NADP. The enzyme had a pH optimum of 7-8.5 (peak, 7.7), was only sparingly soluble in detergents (solubility with Triton X-100 was very poor), and exhibited little latency or change in pH profile in detergent solution. By contrast, rat liver 11 beta HSD was exclusively NADP dependent and was easily solubilized by a wide range of detergents (including Triton X-100), revealing substantial latency and altered pH profile [optimum of 10, becoming 7-10 (peak, 9.5) in detergent]. These data do not merely reflect species differences, as rat placental 11 beta HSD was similar to the human placental isoform. AMP affinity chromatography, which was completely without affinity for rat liver 11 bet…
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“11HSD2 catalyzes only the oxidation of cortisol to cortisone using NAD ϩ and functions with low (nanomolar) concentrations of steroid (K m 10 -100 nM) (581, 582); whether or not 11HSD2 catalyzes reductive reactions remains undemonstrated.”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [581]
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Metadata
- Authors
- Brown, R. W., Chapman, K. E., Edwards, C. R., & Seckl, J. R.
- Affiliations
- Western General Hospital (GB)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1993-06
- Volume
- 132
- Issue
- 6
- Pages
- 2614-2621
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1994741408
- Cited by
- 271
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 5
- FWCI
- 17.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- 11β-hydroxysteroid dehydrogenase, enzyme purification, cortisol, cortisone, placenta, rat liver, subcellular fractionation, detergent solubility, pH optimum
- MeSH terms
- Animals, Chromatography, Affinity, Detergents, Female, Humans, Hydrogen-Ion Concentration, Hydroxysteroid Dehydrogenases, Isoenzymes, Liver, Male, NAD, Placenta, Solubility, Subcellular Fractions, Substrate Specificity, Tissue Distribution, Rats, Wistar, 11-beta-Hydroxysteroid Dehydrogenases, Rats
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