Abstract
One hundred and fifteen rats were ovariectomized, given daily injections of 10 μg of 17β-estradiol 3-benzoate (EB), 250 μg of testosterone propionate (TP), or 10 μg of EB + 250 μg of TP in sesame oil (SO) or SO alone for 1, 1.5 and 2 mo, and heat shocked at 42°C for 15 min. Immediately after heat shock, the increase in inducibly hyperphosphorylated heat shock transcription factor 1 (pHSF1) was highest in TP-treated and least in EB-treated rats. Heat shock transcription factor 1 (HSF1) also accumulated in the nuclei of neurons in TP-treated and exit the nuclei in EB-treated rats. While the subnuclear distribution of HSF1 was uniform and similar in control and heat-shocked EB-treated rats, it localized predominantly on euchromatin in heat-shocked TP-treated rats. An antibody, which preferentially recognized pHSF1, stained almost exclusively cell nuclei and demonstrated irregularly-shaped and round neuronal nuclei of heat-shocked TP- and EB-treated rats, respectively. Concomitantly, synthesis of the inducible heat shock protein Hsp70 was lowest in EB- and highest in TP-treated rats. In this model, testosterone prevents the heat shock-induced hyperphosphorylation of tau. Because HSF1 delays aging, its enhanced activation by testosterone strengthens the argument for a therapeutic role of androgens in Alzheimer's disease.
Get full access to this article
View all access options for this article.