title: Intracrine androgenic apparatus in human bone marrow stromal cells.
abstract: It was suggested that human mesenchymal stromal cells might contain an intracrine enzyme machinery potentially able to synthesize the cell's own supply of dihydrotestosterone (DHT) from dehydroepiandrosterone (DHEA) pro-hormone produced in the adrenal cortex in the reticular zone, which is unique to primates. Indeed, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 5alpha-reductase enzyme proteins were expressed in resting mesenchymal stromal cells (MSCs) in vitro. However, the 'bridging' enzymes 17beta-HSDs, catalysing interconversion between 17beta-ketosteroids and 17beta-hydroxysteroids, were not found in resting MSCs, but 17beta-HSD enzyme protein was induced in a dose-dependent manner by DHEA. Quantitative real-time polymerase chain reactions disclosed that this was mainly due to induction of the isoform 5 catalysing this reaction in 'forward', androgen-bound direction (P < 0.01). This work demonstrates that the MSCs have an intracrine machinery to convert DHEA to DHT if and when challenged by DHEA. DHEA as substrate exerts a positive, feed-forward up-regulation on the 17beta-hydroxy steroid dehydrogenase-5, which may imply that DHEA-DHT tailor-making in MSCs is subjected to chronobiological regulation.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tarvo
authors.initials: T
authors.lastname: Sillat
authors.forename: Raimo
authors.initials: R
authors.lastname: Pöllänen
authors.forename: Joana R C
authors.initials: JR
authors.lastname: Lopes
authors.forename: Pauliina
authors.initials: P
authors.lastname: Porola
authors.forename: Guofeng
authors.initials: G
authors.lastname: Ma
authors.forename: Matti
authors.initials: M
authors.lastname: Korhonen
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002460:Cell Line; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008956:Models, Chemical; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D000728:Androgens; D013196:Dihydrotestosterone; D003687:Dehydroepiandrosterone; D015067:17-Hydroxysteroid Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D042944:Cholestenone 5 alpha-Reductase