Gonadal Hormones And Frontocortical Expression Of Vascular Endothelial Growth Factor In Male Stroke-prone, Spontaneously Hypertensive Rats, A Model For Attention-deficit/hyperactivity Disorder

Gonadal Hormones And Frontocortical Expression Of Vascular Endothelial Growth Factor In Male Stroke-prone, Spontaneously Hypertensive Rats, A Model For Attention-deficit/hyperactivity Disorder

Jesmin S; Togashi H; Sakuma I; Mowa C N; Ueno K I; Yamaguchi T; Yoshioka M; Kitabatake A

Endocrinology

2004

2004-09

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, phosphorylated. Akt (pAkt), estrogen receptor-alpha, aromatase, and capillary density in sham-operated SHRSP were remarkably down-regulated, whereas androgen receptor levels were up-regulated, compared with age-matched genetic control, Wistar-Kyoto rats. Castration, estrogen, and androgen receptor antagonist (flutamide) counteracted these effects. Dihydrotestosterone, but not testosterone, reversed the beneficiary effects of castration. Estrogen receptor-beta levels remained unchanged in all groups examined. We postulate that changes in androgen metabolism that tend to up-regulate local dihydrotestosterone concentration and diminish estrogen 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.

aged female rats; animal-model; central-nervous-system; cerebral-blood-flow; computed tomography; deficit-hyperactivity-disorder; emission; Endocrinology & Metabolism; estrogen-receptor-alpha; in-situ hybridization; insulin-resistant; messenger-ribonucleic-acid; stage

Journal Article or Conference Abstract Publication

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

4330-4343

9

145