Evaluation of the effects of testosterone and luteinizing hormone on regulation of β-amyloid in male 3xTg-AD mice.

Brain Research
Emily R RosarioChristian J Pike

Abstract

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 β-amyloid (Aβ) 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, Aβ 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 Aβ levels. Treatment of GDX mice with testosterone significantly reduced Aβ levels. In contrast, leuprolide did not significantly decrease Aβ levels and moreover, inhibited the Aβ-lowering effect of testosterone. Evaluation of hippocampal-dependent behav...Continue Reading

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Citations

Jan 22, 2013·Pharmacology, Biochemistry, and Behavior·Benjamin Suarez-JimenezAgnès Lacreuse
Jun 3, 2015·Hormones and Behavior·Veronica L Burnham, Janice E Thornton
Sep 15, 2018·Endocrinology·Yang Lei, Zhou Renyuan
May 23, 2019·Journal of Molecular Neuroscience : MN·Taratorn FainantaSuchinda Malaivijitnond
Nov 22, 2016·Journal of Neuroscience Research·Lisa C Golden, Rhonda Voskuhl
Dec 12, 2018·Journal of Alzheimer's Disease : JAD·André de Macêdo Medeiros, Regina Helena Silva
Feb 19, 2019·Journal of Alzheimer's Disease : JAD·Tobore Onojighofia Tobore
Apr 15, 2019·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Tobore Onojighofia Tobore
Jul 11, 2020·International Journal of Molecular Sciences·Yvette Akwa
Jan 19, 2021·Journal of Alzheimer's Disease : JAD·Jessica L DennisonClaes Wahlestedt

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