GABAergic Transmission to Gonadotropin-releasing Hormone (GnRH) Neurons is Regulated by GnRH in a Concentration-dependent Manner Engaging Multiple Signaling Pathways

Overview

Journal J Neurosci

Specialty Neurology

Date 2009 Aug 7

PMID 19657033

Citations 27

Authors

Peilin Chen

Suzanne M Moenter

Affiliations

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Abstract

Gonadotropin-releasing hormone (GnRH) neurons are the central regulators of fertility. GnRH stimulates or inhibits GnRH neuronal activity depending on dose. The mechanisms for these actions remain unknown. We hypothesized GnRH acts in part by altering fast synaptic transmission to GnRH neurons. GABAergic and glutamatergic postsynaptic currents (PSCs), both of which can excite these neurons, were recorded from GnRH neurons in brain slices from adult intact and orchidectomized (ORX) males. ORX enhanced the frequency of GABA transmission to GnRH neurons, but had no effect on glutamatergic transmission. Effects of ORX on GABAergic transmission were reversed by estradiol replacement, suggesting GABA is a mediator of steroid feedback in males. GABAergic neurons express type-1 GnRH receptor (GnRHR-1). Low GnRH (20 nm) reduced GABAergic PSC frequency in GnRH neurons from both ORX and intact mice. High GnRH (2 microm) had no effect on either GABAergic or glutamatergic transmission to GnRH neurons. To investigate mechanisms mediating low-dose GnRH suppression of GABAergic transmission, GABAergic PSCs were recorded after arresting G(alphai) activity with pertussis toxin (PTX). PTX abolished the suppressive effect of low GnRH. Moreover, PTX uncovered a stimulatory effect of high GnRH on GABAergic transmission. These data suggest low-dose GnRH suppresses GnRH firing rate in part by decreasing GABAergic transmission to the GnRH neurons, independent of gonadal hormone milieu. Low-dose GnRH appears to exert the suppressive effect by activating GnRHR-I coupled to G(alphai). The concentration-dependent effects of GnRH may be mediated in part by changes in affinity of GnRH to GnRHR-I coupled to different G(alpha) proteins.

Citing Articles

Gonadal Feedback Alters the Relationship between Action Potentials and Hormone Release in Gonadotropin-Releasing Hormone Neurons in Male Mice.

Chen X, Moenter S J Neurosci. 2023; 43(40):6717-6730.

PMID: 37536982 PMC: 10552940. DOI: 10.1523/JNEUROSCI.2355-22.2023.

The electrophysiologic properties of gonadotropin-releasing hormone neurons.

Constantin S, Moenter S, Piet R J Neuroendocrinol. 2021; 34(5):e13073.

PMID: 34939256 PMC: 9163209. DOI: 10.1111/jne.13073.

Gonadotropin-Releasing Hormone (GnRH) Neuron Potassium Currents and Excitability in Both Sexes Exhibit Minimal Changes upon Removal of Negative Feedback.

DeFazio R, Moenter S eNeuro. 2021; 8(4).

PMID: 34135001 PMC: 8266219. DOI: 10.1523/ENEURO.0126-21.2021.

Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

Dulka E, Moenter S Endocrinology. 2017; 158(11):3943-3953.

PMID: 28938422 PMC: 5695838. DOI: 10.1210/en.2017-00768.

Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.

Vanacker C, Moya M, DeFazio R, Johnson M, Moenter S Endocrinology. 2017; 158(10):3553-3564.

PMID: 28938398 PMC: 5659697. DOI: 10.1210/en.2017-00382.

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