Effects of androgens on endothelial progenitor cells in vitro and in vivo
Gian Paolo Fadini1, Mattia Albiero, Andrea Cignarella
1Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy. gianpaolofadini@hotmail.com
Insights
Androgens like testosterone do not directly impact endothelial progenitor cells in men. While they affect early progenitor cells, overall cardiovascular health appears more linked to oestrogen levels.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Cell Biology
Background:
- Androgen effects on the cardiovascular system are debated.
- Endothelial progenitor cells (EPCs) are crucial for cardiovascular health.
- Oestrogens stimulate EPCs, and androgens may also influence them.
Purpose of the Study:
- To investigate the direct effects of androgens on EPCs.
- To determine the role of testosterone and dihydrotestosterone in EPC biology.
- To examine the relationship between androgen levels and EPCs in men.
Main Methods:
- In vitro studies on human EPCs treated with testosterone and dihydrotestosterone.
- In vivo studies involving castration and androgen replacement in rats.
- Analysis of EPC levels in relation to hormone concentrations in healthy men.
Main Results:
- Testosterone and dihydrotestosterone did not affect late EPCs but modulated early monocytic EPCs in vitro.
- Castration reduced EPCs in rats, and androgen replacement failed to restore normal levels, linked to low oestrogen.
- In healthy men, EPC levels correlated more strongly with oestradiol than testosterone.
Conclusions:
- Androgens do not exert direct effects on EPC expansion and function.
- EPC levels are more closely associated with oestrogen than androgen concentrations.
- The findings suggest a limited direct role for androgens in EPC biology relevant to cardiovascular health.
Abstract:
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.
