Estradiol regulates multiple tetrodotoxin-sensitive sodium currents in gonadotropin releasing hormone neurons: implications for cellular regulation of reproduction

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The gonadotropin releasing hormone (GnRH) neuron is the pivotal control center in a tightly regulated reproductive axis. Estradiol typically has a negative effect on GnRH release, but positive feedback occurs to initiate the luteinizing hormone (LH) surge, resulting in ovulation. We performed electrophysiological recordings in GnRH-enhanced green fluorescent protein neurons dissociated from female mice. The results demonstrate that estradiol can inhibit the transient sodium current and decreases peak current density significantly. Apply estradiol directly to the neurons in the dish revealed that: estradiol appears to regulate the sodium current during the action potential in a time-of-day manner. Current densities from estradiol-treated neurons were significantly smaller than control in the morning (1000-1400 hours), but were significantly larger in amplitude than morning currents in the afternoon (1400-1700 hours). Current density in estradiol-treated neurons increased significantly in afternoon cultures, while currents in control cultures remain unchanged. When the current were examined on an hour-by-hour basis, sodium currents in estradiol-treated neurons remained constant in the AM (1000-1200), and then briefly decreased before dramatically increasing between 1300-1400 hours. This suggests that estradiol negatively feeds back on GnRH neurons in the morning, but positively feeds back in the afternoon, which can result a decrease of cell excitability in the morning, but an increase of cell excitability in the afternoon.