title: Estradiol attenuates multiple tetrodotoxin-sensitive sodium currents in isolated gonadotropin-releasing hormone neurons.
abstract: Secretion from gonadotropin-releasing hormone (GnRH) neurons is necessary for the production of gametes and hormones from the gonads. Subsequently, GnRH release is regulated by steroid feedback. However, the mechanisms by which steroids, specifically estradiol, modulate GnRH secretion are poorly understood. We have previously shown that estradiol administered to the female mouse decreases inward currents in fluorescently labeled GnRH neurons. The purpose of this study was to examine the contribution of sodium currents in the negative feedback action of estradiol. Electrophysiology was performed on GnRH neurons dissociated from young, middle-aged, or old female mice. All mice were ovariectomized; half were estradiol replaced. The amplitude of the sodium current underlying the action potential was significantly decreased in GnRH neurons from young estradiol-treated animals. In addition, in vivo estradiol significantly decreased the transient sodium current amplitude, but prolonged the sodium current inactivation time constant. Estradiol decreased the persistent sodium current amplitude, and induced a significant negative shift in peak current potential. In contrast to results obtained from cells from young reproductive animals, estradiol did not significantly attenuate the sodium current underlying the action potential in cells isolated from middle-aged or old mice. Sodium channels can modulate cell threshold, latency of firing, and action potential characteristics. The reduction of sodium current amplitude by estradiol suggests a negative feedback on GnRH neurons, which could lead to a downregulation of cell excitability and hormone release. The attenuation of estradiol regulation in peripostreproductive and postreproductive animals could lead to dysregulated hormone release with advancing age.
authors.affiliation: Department of Biological Engineering, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Mona
authors.initials: M
authors.lastname: Garro
authors.forename: M Cathleen
authors.initials: MC
authors.lastname: Kuehl-Kovarik
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004967:Estrogens; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; D013779:Tetrodotoxin; D004958:Estradiol