Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated, in part, with male preponderance and reduced regional cerebral blood flow (rCBF). However, mechanism(s) underlying male preponderance and reduced rCBF in AD/HD are unclear. The present study profiles the expression of angiogenic and hormonal factors likely to underlie these symptoms using a recently characterized AD/HD animal model, juvenile male stroke-prone spontaneously hypertensive rats (SHRSP). Because vascular endothelial growth factor (VEGF) signaling cascade and gonadal steroids are key regulators of angiogenesis and gender-based behavior, respectively, we profiled their patterns of expression in the frontal cortex of SHRSP, to elucidate their roles in the genesis of AD/HD male preponderance and rCBF. Interestingly, levels of VEGF, VEGF receptors (KDR, Flt-1), endothelial nitric oxide synthase (eNOS), phosphorylated Akt (pAkt), estrogen receptor- (ER), aromatase and capillary density in sham-operated SHRSP were remarkably down-regulated, whereas androgen receptor (AR) levels were up-regulated, compared with age-matched genetic control, Wistar-Kyoto rats (WKY). Castration, estrogen (E), and AR antagonist (flutamide) counteracted these effects. Dihydrotestosterone (DHT), but not testosterone (Ts), reversed the beneficiary effects of castration. ER levels remained unchanged in all groups examined. We postulate that changes in androgen metabolism that tend to up-regulate local DHT concentration and diminish E synthesis, in the frontal cortex of juvenile male SHRSP, may lower levels and/or activity of VEGF and its signaling cascade, and, subsequently, reduce rCBF. These findings could, in part, help explain the pathogenesis of reduced rCBF and male preponderance in AD/HD.