title: Species differences of 11beta-hydroxysteroid dehydrogenase type 2 function in human and rat term placenta determined via LC-MS/MS.
abstract: BACKGROUND
  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.
  
  
  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 <1. In line with these species-specific findings, human placenta showed a prominent 11β-HSD2 activity, while in rat placenta higher 11β-HSD1 glucocorticoid turnover rates were determined.
  
  
  CONCLUSIONS
  Placental steroid metabolism of human and rat shows relevant species-specific differences, especially regarding the barrier function of 11β-HSD2 at term. The exclusive expression of CRH in the human placenta further points to relevant differences in the regulation of parturition in rats. Consideration of these findings is warranted when transferring results from rodent placental glucocorticoid metabolism into humans.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Heussner
authors.affiliation: Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ruebner
authors.affiliation: Department of Gynecology and Obstetrics, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Huebner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Menendez-Castro
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany. Electronic address: fabian.fahlbusch@uk-erlangen.de.
authors.forename: Fabian B
authors.initials: FB
authors.lastname: Fahlbusch
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rauh
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000328:Adult; D000818:Animals; D002853:Chromatography, Liquid; D003345:Corticosterone / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000032:analysis / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D053719:Tandem Mass Spectrometry; D047929:Term Birth / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D003346:Corticotropin-Releasing Hormone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C003552:11-dehydrocorticosterone; D003345:Corticosterone
keywords: 11beta-hydroxysteroid dehydrogenase; CRH; Glucocorticoid; Human; LC-MS/MS; Microsomes; Placenta; Rat; Steroids