Lack of sex differences in gonadotropin-releasing hormone (GnRH) neuron potassium currents and excitability

Abstract

AbstractGonadotropin-releasing hormone (GnRH) drives pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone, which in turn regulate gonadal functions including steroidogenesis. The pattern of GnRH release and thus fertility depend on gonadal steroid feedback. Under homeostatic (negative) feedback conditions, removal of the gonads from either females or males increases the amplitude and frequency of GnRH release and alters the long-term firing pattern of these neurons in brain slices. The neurobiological mechanisms intrinsic to GnRH neurons that are altered by homeostatic feedback are not well studied and have not been compared between sexes. During estradiol positive feedback, which is unique to females, there are correlated changes in voltage-gated potassium currents and neuronal excitability. We thus hypothesized these same mechanisms would be engaged in homeostatic negative feedback. Voltage-gated potassium channels play a direct role in setting excitability and action potential properties. Whole-cell patch-clamp recordings of GFP-identified GnRH neurons in brain slices from sham-operated and castrated adult female and male mice were made to assess fast (IA) and slow (IK) inactivating potassium currents as well as action potential properties. Surprisingly, no changes were observed in most potassium current properties, input resistance or capacitance and this was reflected in a lack of differences in excitability and specific action potential properties. These results support the concept that, in contrast to positive feedback, steroid negative feedback regulation of GnRH neurons in both sexes is likely conveyed to GnRH neurons via mechanisms that do not induce major changes in the biophysical properties of these cells.Significance StatementThe pattern of activity of gonadotropin-releasing hormone (GnRH) neurons is crucial to reproductive success in both males and females. Direct comparison of GnRH neurons from mice of both sexes during negative feedback and after gonadectomy revealed few differences in potassium currents, excitability, and action potential properties. These results support the hypothesis that neurons presynaptic to GnRH neurons communicate negative feedback to these cells in a manner that does not alter their intrinsic biophysical properties.