Effects of androgens on endothelial progenitor cells in vitro and in vivo.
The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early 'monocytic' endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo.
Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy. gianpaolofadini@hotmail.com
Gian Paolo
GP
Fadini
Mattia
M
Albiero
Andrea
A
Cignarella
Chiara
C
Bolego
Christian
C
Pinna
Elisa
E
Boscaro
Elisa
E
Pagnin
Renzo
R
De Toni
Saula
S
de Kreutzenberg
Carlo
C
Agostini
Angelo
A
Avogaro
D000328:Adult; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001772:Blood Cell Count; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
D000728:Androgens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase