Mitochondrial complex I inhibition depletes plasma testosterone in the rotenone model of Parkinson's disease.
Age-related depletion of testosterone may increase the brain's vulnerability to parkinsonian- or Alzheimer's-like neurodegenerative disorders. In rats, rotenone, a mitochondrial complex I inhibitor, causes specific nigral dopaminergic neurodegeneration producing parkinsonian symptoms. In this study, rotenone was administered on a daily basis (2 mg/kg i.p.) to two groups of rats, over a period of 30 and 60 days, respectively. In order to contribute towards the validation of the rotenone rat model, the changing level of the peripheral sex steroid hormone, testosterone, which would also mimic those found in Parkinson's disease (PD) patients, was evaluated. Parallel to this, prolactin, luteinizing hormone (LH), the nonsexual steroid thyroid-stimulating hormone, and the corticosterone hormone levels in the peripheral blood plasma were measured to show whether other hormones have also been affected by complex I inhibition. The rotenone treatment caused a decrease of testosterone level in the peripheral blood plasma. There were no differences in the thyroid hormone and prolactin but increases in leutinizing hormone and corticosterone were observed. Data from this study indicate that rotenone depleted the sex steroid hormone which is preferentially produced in the periphery, e.g., adrenal gland and testis. In conclusion, because a decrease in testosterone levels is also one of the comorbidities which are found in male PD patients, our results indicate that the rotenone model mimics PD symptoms not only on a neuronal and behavioral level, but also on the testosterone levels.
Alam
M
M
Zoological Institute, Department of Neuropharmacology, Morgenstelle 28E, University of Tuebingen, 72076 Tuebingen, Germany.
Schmidt
W J
WJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D010300:Parkinson Disease / Q000097:blood* / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
D007306:Insecticides; D012402:Rotenone; D013739:Testosterone; D000255:Adenosine Triphosphate