Reference - Detail
| RRC ID | 95 |
|---|---|
| Author | Jesmin S, Togashi H, Sakuma I, Mowa CN, Ueno K, Yamaguchi T, Yoshioka M, Kitabatake A. |
| Title | Gonadal hormones and frontocortical expression of vascular endothelial growth factor in male stroke-prone, spontaneously hypertensive rats, a model for attention-deficit/hyperactivity disorder. |
| Journal | Endocrinology |
| Abstract |
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. |
| Volume | 145(9) |
| Pages | 4330-43 |
| Published | 2004-9-1 |
| DOI | 10.1210/en.2004-0487 |
| PII | en.2004-0487 |
| PMID | 15178644 |
| MeSH | Animals Aromatase / genetics Attention Deficit Disorder with Hyperactivity / physiopathology* Capillaries / physiology Cerebrovascular Circulation / physiology Dihydrotestosterone / blood Disease Models, Animal Estrogen Receptor alpha Estrogen Receptor beta Estrogens / blood Frontal Lobe / blood supply* Gonadal Steroid Hormones / blood* Hypertension / physiopathology* Male Nitric Oxide / metabolism Nitric Oxide Synthase / genetics Nitric Oxide Synthase Type III Protein Serine-Threonine Kinases / genetics Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins c-akt Rats Rats, Inbred SHR Rats, Inbred WKY Receptors, Androgen / genetics Receptors, Estrogen / genetics Signal Transduction / physiology Stroke / physiopathology Testosterone / blood Vascular Endothelial Growth Factor A / genetics* Vascular Endothelial Growth Factor Receptor-1 / genetics Vascular Endothelial Growth Factor Receptor-2 / genetics |
| IF | 3.934 |
| Times Cited | 20 |
| WOS Category | ENDOCRINOLOGY & METABOLISM |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Rats | WKY/Ezo(strainID=568) SHRSP/Ezo(strainID=357) |