Ovarian steroids and raloxifene prevent MPTP-induced dopamine depletion in mice.
The activity of steroids was studied in 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned retired breeder C57BL/6 male mice as a model of Parkinson's disease. Steroids were injected daily for 5 days before MPTP (4 injections, 15 mg/kg i.p., at 2 h intervals) and hormonal treatment continued for 5 more days. Mice that received 17beta-estradiol or progesterone or raloxifene (a selective estrogen receptor modulator) and MPTP had striatal concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) similar to those in control animals, whereas mice that received MPTP alone or with 17alpha-estradiol (the isomer with weak estrogenic activity) had an extensive decrease of DA and its metabolites. These results suggest stereospecific prevention of MPTP-induced dopamine loss by 17beta-estradiol, which is also observed with progesterone and raloxifene.
Grandbois
M
M
Oncology and Molecular Endocrinology Research Center, Laval University Medical Center, Sainte-Foy, Québec, Canada.
Morissette
M
M
Callier
S
S
Di Paolo
T
T
D000818:Animals; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004967:Estrogens / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013237:Stereoisomerism
D015259:Dopamine Agents; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004298:Dopamine