Table 1.
Effects of androgens on functions of the cerebral vasculature
| Function | Subjects/cells | Androgen | Results | Reference |
|---|---|---|---|---|
| Angiogenesis | EPC (healthy male donors) | Methyltrienolone (synthetic androgen) | Dose-dependent increase in proliferation, migration and colony formation. Effect is AR-dependent (blocked by flutamide). | Foresta et al. [29] |
| Angiogenesis | EPC (healthy male donors) | DHT | Dose- and time-dependent increase in VEGF and proliferative, migratory, and adhesive abilities of EPCs. Via RhoA/ROCK pathway. | Zhang et al. [30] |
| Angiogenesis | EPC (healthy male donors) | DHT | Dose- and time-dependent increase in proliferative activity and adhesive ability of EPCs. The PI3-K/Akt pathway plays a role. | Liu et al. [31] |
| Angiogenesis | Healthy adult males | N/A | T/E2 ratio negatively correlated with number of EPCs. | Fadini et al. [32] |
| Angiogenesis | EPC (healthy male donors) | T or DHT | No effect on expansion and function of late EPCs; increase generation of early EPCs | Fadini et al. [32] |
| Angiogenesis | Adult male SD rats (intact & GDX) | T or DHT replacement | T & DHT replacement unable to restore reduced EPC levels in GDX males | Fadini et al. [32] |
| Angiogenesis | Adult female canaries | T | Increased angiogenesis and endothelial BDNF, VEGF, and VEGF-R in the brain | Louissaint et al. [33] |
| Cerebrovascular reactivity | Adult male Fisher 344 rats (intact & GDX) | T replacement | Endothelium-dependent myogenic tone is reduced in GDX rats, which is NOS-independent and reversed by T replacement. | Geary et al. [34] |
| Cerebrovascular reactivity | Adult male Fisher 344 rats (GDX) | T replacement | T replacement increased vascular tone in endothelium-dependent manner of isolated MCA, independent of COX, NOS, and endothelin. Effect may be through suppression of EDHF-like vasodilator. | Gonzales et al. [35] |
| Cerebrovascular reactivity | Adult male Fisher 344 rats (GDX) | T replacement | T replacement increased vascular tone of MCA, likely by increasing synthesis of thromboxane A2. | Gonzales et al. 2005 [36] |
| BBB function and inflammation | Adult male C57BL/6J mice (intact & GDX) | T replacement | GDX increased BBB permeability and inflammation; reduced EC TJ proteins. Effects reversed by T replacement. | Atallah et al. [37] |
| Blood-spinal cord barrier | Young adult male Wistar rats | T | T treatment decreased some TJ proteins in spinal cord and increased P-gp expression. | Nierwinska et al. [38] |
| Inflammation | Adult male Wistar rats (GDX) | DHT replacement | DHT stimulated CBV inflammation by increasing COX-2, iNOS, and NFkB levels in cerebral arteries (ex vivo and in vivo). Effect is AR-dependent (blocked by flutamide). | Gonzales et al. [39] |
| Inflammation | Adult male Wistar rats (GDX) | DHT (in vivo or ex vivo) | DHT increases COX-2 under normoxia but decreases COX-2 under hypoxia in cerebral arteries. DHT blunts HIF-1a following hypoxia. | Zuloaga & Gonzales [40] |
| Inflammation | Primary human brain VSMC | DHT | DHT increases COX-2 under normoxia but decreases COX-2 under hypoxia. DHT blunts HIF-1a following hypoxia (AR-independent). | Zuloaga & Gonzales [40] |
| Inflammation | Primary human brain VSMC | DHT | Anti-inflammatory effect of DHT (reduction of COX-2) is mediated by ER-beta, likely via conversion to 3β-diol | Zuloaga et al. [22] |
| Inflammation | Adult male Fisher 344 rats (intact & GDX) | T (in vivo) or ex vivo T treatment | T increases LPS-induced CBV inflammation (COX-2, iNOS, PGE2). | Razmara et al. [41] |
| EC senescence | Adult male SAMP8, control SAMR 1 mice | DHT | DHT treatment decreases hippocampal endothelial cell senescence. | Ota et al. [42] |