title: Androgens Prevent the Heat Shock-Induced Hyperphosphorylation but not Dephosphorylation of t in Female Rats. Implications for Alzheimer's Disease.
abstract: We have previously shown that heat shock induces rapid dephosphorylation of tau in both female and male rats followed by hyperphosphorylation only in female rats (J Neurochem 66 (1996), 1140-1149). We have also shown that the heat shock-induced hyperphos-phorylation of tau is estrogen-independent in female rats and prevented by androgens in male rats (Proc Natl Acad Sci USA 94 (1997), 6612-6617). To investigate whether androgens could prevent the hyperphosphorylation of tau also in female rats, twenty-three 2- to 3-month-old Sprague-Dawley rats were ovariectomized and given daily subcutaneous injections of 1 mg/250 g of testosterone propionate for 3-5 weeks. Immunoblots of SDS cerebral extracts were analysed qualitatively using the peroxidase-antiperoxidase technique and phosphate-dependent and -independent anti-tau antibodies, and quantitatively using Tau-1 and 125I-labeled protein A. We have found that while at 0 h after heat shock tau was dephosphorylated, at 3 h and 6 h after heat shock tau was not hyperphosphorylated, as would be the case in non-androgen-treated female rats (ref. above). In addition, tau became dephosphorylated in non-heat-shocked control rats. Because tau is abnormally hyperphosphorylated in Alzheimer's disease, the possibility of using combined estrogen/androgen replacement therapy in postmenopausal women as a preventive measure against Alzheimer's disease should be investigated.
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
authors.forename: S.C.
authors.initials: SC
authors.lastname: Papasozomenos
authors.forename: T.
authors.initials: T
authors.lastname: Papasozomenos