| First Author | Rosario ER | Year | 2012 |
| Journal | Brain Res | Volume | 1466 |
| Pages | 137-45 | PubMed ID | 22587890 |
| Mgi Jnum | J:186440 | Mgi Id | MGI:5432315 |
| Doi | 10.1016/j.brainres.2012.05.011 | Citation | Rosario ER, et al. (2012) Evaluation of the effects of testosterone and luteinizing hormone on regulation of beta-amyloid in male 3xTg-AD mice. Brain Res 1466:137-45 |
| abstractText | During normal aging, men experience a significant decline in testosterone levels and a compensatory elevation in levels of gonadotropin luteinizing hormone (LH). Both low testosterone and elevated LH have been identified as significant risk factors for the development of Alzheimer's disease (AD) in men. It is unclear whether changes in testosterone or LH primarily underlie the relationship with AD, and therefore may be a more suitable therapeutic target. To examine this issue, we compared levels of beta-amyloid (Abeta) immunoreactivity in male 3xTg-AD mice under varying experimental conditions associated with relatively low or high levels of testosterone and/or LH. In gonadally intact mice, Abeta accumulation increased after treatment with the gonadotropin-releasing hormone agonist leuprolide, which inhibits the hypothalamic-pituitary-gonadal (HPG) axis and reduces both testosterone and LH levels. In gonadectomized (GDX) mice with low testosterone and high LH, we also observed increased Abeta levels. Treatment of GDX mice with testosterone significantly reduced Abeta levels. In contrast, leuprolide did not significantly decrease Abeta levels and moreover, inhibited the Abeta-lowering effect of testosterone. Evaluation of hippocampal-dependent behavior revealed parallel findings, with performance in GDX mice improved by testosterone but not leuprolide. These data suggest that Abeta-lowering actions of testosterone are mediated directly by androgen pathways rather than indirectly via regulation of LH and the HPG axis. These findings support the clinical evaluation of androgen therapy in the prevention and perhaps treatment of AD in hypogonadal men. |
