Premium
Lack of Effect of Testosterone and Dihydrotestosterone Compared to 17β‐Oestradiol in 1‐Methyl‐4‐Phenyl‐1,2,3,6, Tetrahydropyridine‐Mice
Author(s) -
Ekue A.,
Boulanger J.F.,
Morissette M.,
Di Paolo T.
Publication year - 2002
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2002.00833.x
Subject(s) - mptp , endocrinology , medicine , dopamine , homovanillic acid , dopamine transporter , chemistry , dihydrotestosterone , testosterone (patch) , vesicular monoamine transporter , substantia nigra , 3,4 dihydroxyphenylacetic acid , monoamine neurotransmitter , androgen , hormone , dopaminergic , biology , receptor , serotonin
Previous work from our laboratory has demonstrated prevention of 1‐methyl‐4‐phenyl‐1,2,3,6, tetrahydropyridine (MPTP)‐induced striatal dopamine depletion in C57Bl/6 mice by 17β‐oestradiol, progesterone and raloxifene. The activity of androgenic compounds in MPTP mice has received less attention and was the object of the present investigation. The effects of 17β‐oestradiol (2 µg/day), testosterone (100 µg/day) and dihydrotestosterone (DHT) (2 µg/day or 100 µg/day) were studied during 5 days before and after an acute treatment of four MPTP (10 mg/kg) injections in male C57Bl/6 mice. Striatal concentrations of dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid were measured by high‐performance liquid chromatography. MPTP mice treated with saline showed large decreases in dopamine and its metabolites compared to control mice. 17β‐oestradiol partially spared this decrease whereas testosterone and DHT did not. Striatal specific binding to the dopamine transporter (DAT) and to the vesicular monoamine transporter (VMAT 2 ) were measured using [ 125 I] RTI‐121 and [ 3 H] dihydrotetrabenazine autoradiography, respectively. As with striatal dopamine concentrations, MPTP treatment caused a decrease in DAT and VMAT 2 specific binding. 17β‐oestradiol partially spared this decrease, whereas androgens did not. In the substantia nigra, DAT mRNA was measured by in situ hybridization. MPTP treatment induced a significant, but smaller decrease in substantia nigra DAT mRNA than striatal DAT protein. In addition, 17β‐oestradiol completely prevented the MPTP‐induced decrease of DAT mRNA, whereas androgens did not. The present results show that androgens are unable to protect against MPTP‐induced dopaminergic toxicity.