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...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2009-09, Vol.13 (9b), p.3296-3302
Main Authors: Sillat, Tarvo, Pöllänen, Raimo, Lopes, Joana R.C., Porola, Pauliina, Ma, Guofeng, Korhonen, Matti, Konttinen, Yrjö T.
Format: Article
Language:English
Subjects:
17-Hydroxysteroid Dehydrogenases - metabolism
5α‐reductase
Androgens - metabolism
Bone marrow
Bone Marrow Cells - cytology
Cell Differentiation
Cell Line
Cells
Cholestenone 5 alpha-Reductase - metabolism
dehydroepiandrosterone
Dehydroepiandrosterone - metabolism
dihydrotestosterone
Dihydrotestosterone - pharmacology
Enzymes
Fibroblasts - metabolism
Gene expression
Gene Expression Regulation
Hormones
human bone marrow stromal cells
Humans
hydroxysteroid dehydrogenase
Hydroxysteroid Dehydrogenases - metabolism
Immunohistochemistry - methods
intracrinology
Models, Chemical
Polymerase chain reaction
Stromal Cells - cytology
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Summary: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, 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 5α‐reductase enzyme proteins were expressed in resting mesenchymal stromal cells (MSCs) in vitro. However, the ‘bridging’ enzymes 17β‐HSDs, catalysing interconversion between 17β‐ketosteroids and 17β‐hydroxysteroids, were not found in resting MSCs, but 17β‐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 17β‐hydroxy steroid dehydrogenase‐5, which may imply that DHEA‐DHT tailor‐making in MSCs is subjected to chronobiological regulation.
ISSN:1582-1838
1582-4934
DOI:10.1111/j.1582-4934.2009.00729.x