Species differences of 11beta-hydroxysteroid dehydrogenase type 2 function in human and rat term placenta determined via LC-MS/MS

Abstract Introduction Glucocorticoid-induced fetal programming has been associated with negative metabolic and cardiovascular sequelae in the adult. The placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus from maternal glucocorticoid excess by catalyzing the conv...

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Bibliographic Details
Published in:Placenta (Eastbourne) 2016-01, Vol.37, p.79-84
Main Authors: Heussner, Kirsten, Ruebner, Matthias, Huebner, Hanna, Rascher, Wolfgang, Menendez-Castro, Carlos, Hartner, Andrea, Fahlbusch, Fabian B, Rauh, Manfred
Format: Article
Language:English
Subjects:
11-beta-Hydroxysteroid Dehydrogenase Type 2 - chemistry
11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism
11-beta-Hydroxysteroid Dehydrogenase Type 2 - physiology
11beta-hydroxysteroid dehydrogenase
Adult
Animals
Chromatography, Liquid
Corticosterone - analogs & derivatives
Corticosterone - analysis
Corticosterone - metabolism
Corticotropin-Releasing Hormone - analysis
Corticotropin-Releasing Hormone - metabolism
CRH
Female
Glucocorticoid
Glucocorticoids - analysis
Glucocorticoids - metabolism
Human
Humans
Internal Medicine
LC-MS/MS
Microsomes
Obstetrics and Gynecology
Placenta
Placenta - chemistry
Placenta - enzymology
Placenta - metabolism
Pregnancy
Rat
Rats
Rats, Wistar
Species Specificity
Steroids
Tandem Mass Spectrometry
Term Birth - metabolism
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Summary:Abstract Introduction Glucocorticoid-induced fetal programming has been associated with negative metabolic and cardiovascular sequelae in the adult. The placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus from maternal glucocorticoid excess by catalyzing the conversion of these hormones into biologically inactive derivatives. In vivo experiments addressing placental barrier function are mostly conducted in rodents. Therefore we set out to characterize species-specific differences of rat and human placental 11β-HSD2 steroid turnover, introducing Liquid Chromatography Tandem Mass-Spectrometry (LC-MS/MS) as a tool for rat tissue analysis. Materials and Methods Using LC-MS/MS we determined corticotropin-releasing hormone (CRH), cortisol (F), cortisone (E), corticosterone (B) and 11-dehydrocorticosterone (A) in human and rat placenta at term and measured the enzymatic 11β-HSD glucocorticoid conversion-rates in placental microsomes of both species. In parallel, further glucocorticoid derivatives and sex steroids were determined in the same placental samples. Results In contrast to the human placenta, we did not detect CRH in the rat placenta. While cortisol (F) and cortisone (E) were exclusively present in human term placenta (E/F-ratio >1), rat placenta showed significant levels of corticosterone (B) and 11-dehydrocorticosterone (A), with an A/B-ratio
ISSN:0143-4004
1532-3102
DOI:10.1016/j.placenta.2015.11.009