The activation of heat shock transcription factor 1 is differentially regulated in the brain of estrogen- and testosterone-treated heat-shocked rats.
One hundred and fifteen rats were ovariectomized, given daily injections of 10 microg of 17beta-estradiol 3-benzoate (EB), 250 microg of testosterone propionate (TP), or 10 microg of EB + 250 microg of TP in sesame oil (SO) or SO alone for 1, 1.5 and 2 mo, and heat shocked at 42 degrees 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.
Papasozomenos
Sozos Ch
SCh
Department of Pathology and Laboratory Medicine, The University of Texas-Houston Medical School, Houston, TX 77030, USA. Sozos.C.Papasozomenos@uth.tmc.edu
Papasozomenos
Harry
H
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D022041:Euchromatin / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000187:drug effects* / Q000235:genetics*; D020249:Hormone Replacement Therapy; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D022041:Euchromatin; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D014157:Transcription Factors; D013739:Testosterone; D004958:Estradiol