Get access

Lack of Effect of Testosterone and Dihydrotestosterone Compared to 17β-Oestradiol in 1-Methyl-4-Phenyl-1,2,3,6, Tetrahydropyridine-Mice

Authors

  • A. Ekue,

    1. Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada.
    Search for more papers by this author
  • J.-F. Boulanger,

    1. Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada.
    Search for more papers by this author
  • M. Morissette,

    1. Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada.
    Search for more papers by this author
  • T. Di Paolo

    1. Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada.
    Search for more papers by this author

Thérèse Di Paolo, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, 2705, Laurier Boulevard, Québec, Qc, G1V 4G2, Canada (e-mail: therese.dipaolo@crchul.ulaval.ca).

Abstract

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 (VMAT2) were measured using [125I] RTI-121 and [3H] dihydrotetrabenazine autoradiography, respectively. As with striatal dopamine concentrations, MPTP treatment caused a decrease in DAT and VMAT2 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.

Ancillary