Androgens stimulate endothelial progenitor cells through an androgen receptor-mediated pathway.
OBJECTIVE
Testosterone (T) treatment has recently been shown to induce an increase in the number of endothelial progenitor cells (EPCs) through a possible effect on bone marrow. Hypogonadotrophic hypogonadal (HH) men have low circulating EPCs that increase significantly after T treatment. Moreover, expression of the androgen receptor (AR) has been demonstrated by immunohistochemistry in these cells, suggesting that T might also have a direct effect on EPC function. In the present study we investigated the expression and function of the AR in human EPCs and the in vitro effect of androgens on EPC function. Design and patients EPCs obtained from healthy male anonymous blood donors were analysed after androgen stimulation with and without AR antagonist administration (flutamide).


RESULTS
Reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence analyses demonstrated the expression of AR mRNA and protein in human EPCs. Stimulation of these cells with the synthetic androgen methyltrienolone (R1881) caused AR translocation in the nucleus, suggesting its activation. Colony forming unit (CFU), proliferation and migration assays under different doses of R1881 demonstrated a dose-dependent increase in EPC proliferation, migration and colony formation. All these effects are abolished by flutamide pretreatment.


CONCLUSIONS
This study showed that the increase in the proliferation, migration and colony formation activity of EPCs induced by androgens is an AR-mediated pathway. Androgen exerts these effects at concentrations that are physiologically present in men and therefore further studies are needed to clarify the clinical significance of these effects in normal and pathological conditions.
Foresta
Carlo
C
Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, University of Padova, Padova, Italy. carlo.foresta@unipd.it
Zuccarello
Daniela
D
De Toni
Luca
L
Garolla
Andrea
A
Caretta
Nicola
N
Ferlin
Alberto
A
D000728:Androgens / Q000494:pharmacology*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*