Intracrine androgenic apparatus in human bone marrow stromal cells.
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.
Sillat
Tarvo
T
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Pöllänen
Raimo
R
Lopes
Joana R C
JR
Porola
Pauliina
P
Ma
Guofeng
G
Korhonen
Matti
M
Konttinen
Yrjö T
YT
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*
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