scholarly journals Gonadotropin-releasing hormone (GnRH) neuron potassium currents and excitability in both sexes exhibit minimal changes upon removal of negative feedback

eNeuro ◽  
2021 ◽  
pp. ENEURO.0126-21.2021
Author(s):  
R. Anthony DeFazio ◽  
Suzanne M. Moenter
2021 ◽  
Author(s):  
R Anthony DeFazio ◽  
Suzanne M Moenter

Gonadotropin-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.


1989 ◽  
Vol 67 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Richard F. Weick ◽  
Vaclav Pitelka ◽  
David L. Thompson

Experiments were performed to study the responsiveness of the pituitary to gonadotropin-releasing hormone (GnRH) during the dynamic changes in gonadotropin secretion associated with the estrogen-induced luteinizing hormone (LH) surge in the ovariectomized (OVX) rhesus monkey. Silastic capsules filled with estradiol-17-β were implanted subcutaneously in ovariectomized rhesus monkeys, resulting in an initial lowering of circulating LH and follicle-stimulating hormone (FSH) concentrations followed by an LH–FSH surge. GnRH was injected intravenously just before estrogen implantation, during the negative feedback response and during the rising, the peak, and the declining phases of the LH surge. The LH and FSH responses during the negative feedback phase were as large as those before estrogen treatment (control responses). During the rising phase of the LH surge, the acute response to GnRH injection did not differ significantly from the control response, but the responses 60 and 120 min after injection were somewhat increased. During the declining phase of the LH surge, the pituitary was not responsive to exogenous GnRH, although LH probably continued to be secreted at this time since the LH surge decreased more slowly than predicted by the normal rate of disappearance of LH in the monkey. We conclude that an increased duration of response to GnRH may be an important part of the mechanism by which estrogen induces the LH surge, but we do not see evidence of increased sensitivity of the pituitary to GnRH as an acute releasing factor at that time.Key words: LH surge, GnRH, FSH, ovariectomized monkey.


2017 ◽  
Vol 38 (5) ◽  
pp. 1249-1263 ◽  
Author(s):  
Caroline Adams ◽  
Wylie Stroberg ◽  
Richard A. DeFazio ◽  
Santiago Schnell ◽  
Suzanne M. Moenter

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