Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice

J Neuroendocrinol. 2002 Sep;14(9):731-6. doi: 10.1046/j.1365-2826.2002.00833.x.


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 17beta-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 17beta-oestradiol (2 microg/day), testosterone (100 microg/day) and dihydrotestosterone (DHT) (2 microg/day or 100 microg/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. 17beta-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. 17beta-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, 17beta-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Autoradiography
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism
  • Cocaine / pharmacology
  • Dihydrotestosterone / pharmacology*
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Estradiol / pharmacology*
  • Gonadal Steroid Hormones / pharmacology*
  • Homovanillic Acid / metabolism
  • In Situ Hybridization
  • Iodine Radioisotopes
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / metabolism
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins*
  • Neuropeptides*
  • RNA, Messenger / analysis
  • Testosterone / pharmacology*
  • Tetrabenazine / analogs & derivatives*
  • Tetrabenazine / metabolism
  • Tetrabenazine / pharmacology
  • Tritium
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins


  • Dopamine Plasma Membrane Transport Proteins
  • Gonadal Steroid Hormones
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • RNA, Messenger
  • Slc18a2 protein, mouse
  • Slc6a3 protein, mouse
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • Dihydrotestosterone
  • Tritium
  • 3,4-Dihydroxyphenylacetic Acid
  • RTI 121
  • dihydrotetrabenazine
  • Testosterone
  • Estradiol
  • Cocaine
  • Dopamine
  • Homovanillic Acid
  • Tetrabenazine