Androgens Prevent the Heat Shock-Induced Hyperphosphorylation but not Dephosphorylation of t in Female Rats. Implications for Alzheimer's Disease.
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.
Papasozomenos
S.C.
SC
Department of Pathology and Laboratory Medicine, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
Papasozomenos
T.
T