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11Beta-hydroxysteroid dehydrogenase expression in first trimester human trophoblasts
F Arcuri1, S Sestini, L Paulesu
1Institute of Pathological Anatomy and Histology, University of Siena, Italy.
Molecular and Cellular Endocrinology
|September 2, 1998
Summary
First-trimester human placenta chorionic villi primarily express 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the NAD-dependent isoform. This enzyme activity regulates embryonic glucocorticoid exposure and trophoblast invasion.
Area of Science:
- Reproductive biology
- Endocrinology
- Biochemistry
Background:
- 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes are crucial for regulating glucocorticoid activity.
- Two main isoforms, 11beta-HSD1 (oxoreductase) and 11beta-HSD2 (dehydrogenase), exhibit distinct tissue distribution and cofactor dependencies.
- The role of 11beta-HSD activity in early human placental development and its impact on embryonic exposure to glucocorticoids requires further elucidation.
Purpose of the Study:
- To evaluate the levels and enzymatic characteristics of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in first-trimester human placental chorionic villi.
- To determine the predominant 11beta-HSD isoform expressed in early placental tissue.
- To investigate the functional implications of 11beta-HSD activity in the placenta.
Main Methods:
- Isolation of chorionic villi from first-trimester human placenta.
- Enzymatic assays using corticosterone and 11-dehydrocorticosterone with NAD/NADP and NADH/NADPH.
- Reverse transcription-polymerase chain reaction (RT-PCR) to assess mRNA expression of 11beta-HSD isoforms.
- Immunohistochemical staining to localize 11beta-HSD protein expression.
Main Results:
- A predominant NAD-dependent dehydrogenase activity (11beta-HSD2) was observed, with NAD significantly increasing corticosterone conversion.
- NADP was ineffective in promoting conversion, and no reductase activity (conversion of 11-dehydrocorticosterone to corticosterone) was detected with NADH or NADPH.
- RT-PCR confirmed high mRNA levels for 11beta-HSD2 and undetectable levels for 11beta-HSD1. Immunohistochemistry localized 11beta-HSD2 protein to syncytiotrophoblasts and cell columns.
Conclusions:
- First-trimester human chorionic villi predominantly express the 11beta-HSD2 isoform, indicating significant oxidative activity.
- The trophoblast-associated 11beta-HSD2 activity likely plays a critical role in modulating embryonic exposure to active glucocorticoids during early gestation.
- This enzymatic activity may also be involved in regulating trophoblast invasion of the uterine wall.