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Sex Steroid Levels and AD ‐Like Pathology in 3x T g AD Mice
Author(s) -
Overk C. R.,
Perez S. E.,
Ma C.,
Taves M. D.,
Soma K. K.,
Mufson E. J.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2012.02374.x
Subject(s) - medicine , endocrinology , testosterone (patch) , androgen receptor , androgen , hippocampal formation , hippocampus , sex steroid , genetically modified mouse , amygdala , receptor , biology , hormone , transgene , steroid , biochemistry , prostate cancer , cancer , gene
Decreases in testosterone and 17β‐oestradiol ( E 2 ) are associated with an increased risk for A lzheimer's disease ( AD ), which has been attributed to an increase in β‐amyloid and tau pathological lesions. Although recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD ‐like pathology, almost none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age‐related changes in testosterone and E 2 concentrations, as well as androgen receptor ( AR ) and oestrogen receptor ( ER ) α and β expression, in brain regions displaying AD pathology in intact male and female 3x T g AD and nontransgenic (ntg) mice. We report for the first time that circulating and brain testosterone levels significantly increase in male 3x T g AD mice with age, but without changes in AR ‐immunoreactive (IR) cell number in the hippocampal CA 1 or medial amygdala. The age‐related increase in hippocampal testosterone levels correlated positively with increases in the conformational tau isoform, A lz50. These data suggest that the over‐expression of human tau up‐regulate the hypothalamic‐pituitary‐gonadal axis in these mice. Although circulating and brain E 2 levels remained stable with age in both male and female 3x T g AD and ntg mice, ER ‐IR cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Furthermore, E 2 levels were significantly higher in the hippocampus than in serum, suggesting local production of E 2 . Although triple transgenic mice mimic AD ‐like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions.