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Table 1 Effects of androgens on functions of the cerebral vasculature

From: Androgens’ effects on cerebrovascular function in health and disease

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]