Effect of estradiol on striatal dopamine activity of female hemiparkinsonian monkeys.
A higher prevalence and incidence of Parkinson's disease is observed in men, and beneficial motor effects of estrogens are observed in parkinsonian women. In rodents, an effect of estradiol on dopamine systems is documented, whereas much less is known in monkeys. Enkephalin was shown to exert a compensatory modulatory effect on the denervated dopamine nigrostriatal pathway in monkeys and in humans. Moreover in rodents, striatal preproenkephalin mRNA is increased by estrogen treatment. Hence, we investigated the responsiveness of striatal dopamine to estradiol in long-term ovariectomized monkeys bearing a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic parkinsonian postmenopausal women. Seven ovariectomized female monkeys received a unilateral MPTP lesion; 4 years after ovariectomy, three received 1-month treatment with 17beta-estradiol and the others received vehicle. The lesioned striata showed extensive denervation in all monkeys as measured with dopamine and metabolite concentrations assayed by high-performance liquid chromatography and by autoradiography of the dopamine transporter. The lesioned and intact striata of estradiol-treated monkeys had increased 3-methoxytyramine, and lesioned putamen increased dopamine concentrations compared with vehicle-treated monkeys. Estradiol treatment increased the dopamine transporter in subregions of the intact caudate and putamen compared with the intact striata of vehicle-treated monkeys, but not in the lesioned striata. Preproenkephalin mRNA levels measured by in situ hybridization were increased in the lesioned striata of vehicle treated monkeys and were not further enhanced in estradiol-treated monkeys. These results show that long after ovariectomy, modeling postmenopausal hormonal conditions, brain dopamine metabolism, and transporter are still responsive to estradiol.
Morissette
Marc
M
Molecular Endocrinology and Oncology Research Center, Faculty of Pharmacy, Laval University, CHUL, Quebec City, Canada.
Di Paolo
Thérèse
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001345:Autoradiography; D001679:Biogenic Amines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D008252:Macaca fascicularis; D010052:Ovariectomy; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger
D001679:Biogenic Amines; D050483:Dopamine Plasma Membrane Transport Proteins; D004745:Enkephalins; D004967:Estrogens; D007457:Iodine Radioisotopes; D011498:Protein Precursors; D012333:RNA, Messenger; D004958:Estradiol; C033660:preproenkephalin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C001746:3-methoxytyramine; D004298:Dopamine