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Estrogen Dependent Response to Nicotine in Substantia Nigra and Ventral Tegmental Area of OVX female rats

The incidence of Parkinson's disease is higher in men than women and nicotine (Nic) reduces the risk. To study the interaction between Nic and estrogen (E), OVX rats were treated for 16 days with estradiol benzoate (EB) or vehicle and received Nic injections on days 13–16 (twice daily). Tyrosine hydroxylase (TH) and GTP cyclohydrolase (GTPCH) mRNA levels were determined by qRT‐PCR in VTA and SN. The VTA of OVX rats was especially susceptible to the lowest dose of Nic. In contrast, with EB treatment, only the highest dose of Nic was effective. In SN, both doses of Nic did not change TH mRNA levels in OVX rats with or without EB injections, but EB treatment increased sensitivity of GTPCH gene to Nic. To determine whether E can modulate Nic triggered transcriptional regulation of TH and GTPCH genes, dopaminergic MN9D cells were co‐transfected with pGTPCH/Luc and expression vector for ERa or ERβ. The results revealed that Nic and E elevated GTPCH promoter activity with both ERa and ERβ. The response was reduced with Nic and E combined. The findings provide insight for specificity of Nic regulation of catecholamine and tetrahydrobiopterin biosynthesis in DA neurons in gender specific fashion.