title: 17β-Estradiol regulates the gene expression of voltage-gated sodium channels: role of estrogen receptor α and estrogen receptor β.
abstract: Estradiol (E2) plays a key role in pain modulation, and the biological effects of E2 are transduced by binding estrogen receptors (ERs). Voltage-gated sodium (Nav) channels are responsible for the generation and propagation of action potentials in the membranes of most neurons and excitable cells. Adult dorsal root ganglion (DRG) neurons can express the ERs (ERα and ERβ), and Nav channels (TTX-S: Nav1.1, Nav1.6, and Nav1.7; and TTX-R: Nav1.8, and Nav1.9). Although E2 modulates Nav channel currents, little is known about the molecular mechanisms involved. In this study, we investigate the mRNA expressions of Nav channel subtypes mediated differentially by the ERs in the DRGs of wild-type (WT) and estrogen receptor knockout (αERKO and βERKO) mice. By means of quantitative real-time PCR, we found that the expressions of Nav1.1, Nav1.7, Nav1.8, and Nav1.9 subtypes were elevated in αERKO and βERKO mice, whereas Nav1.6 mRNA decreased in αERKO, but not in βERKO mice. The mRNA expressions of Nav subtypes were increased in E2-treated WT ovariectomized animals. We also found that E2-regulation of Nav1.1 and Nav1.9 mRNA expressions is dependent on ERα, ERβ, and another ER, whereas E2-regulation of Nav1.8 appears to be in an ERβ-dependent manner.
authors.affiliation: Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Peizhi
authors.initials: P
authors.lastname: Wang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010052:Ovariectomy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D015222:Sodium Channels; D004958:Estradiol