Ghrelin Decreases Firing Activity of Gonadotropin-Releasing Hormone (GnRH) Neurons in an Estrous Cycle and Endocannabinoid Signaling Dependent Manner

Imre Farkas, Csaba Vastagh, Miklós Sárvári, Z. Liposits

Research output: Article

27 Citations (Scopus)

Abstract

The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R) in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca2+-imaging revealed a ghrelin-triggered increase of the Ca2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10μM) suggesting direct action of ghrelin. Estradiol (1nM) eliminated the ghrelin-evoked rise of Ca2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40nM-4μM) administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1) antagonist AM251 (1μM) and the intracellularly applied DAG-lipase inhibitor THL (10μM), indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

Original languageEnglish
Article numbere78178
JournalPLoS One
Volume8
Issue number10
DOIs
Publication statusPublished - okt. 4 2013

Fingerprint

Endocannabinoids
ghrelin
Ghrelin
Estrous Cycle
gonadotropin-releasing hormone
Gonadotropin-Releasing Hormone
estrous cycle
Neurons
neurons
Ghrelin Receptor
mice
calcium
estradiol
antagonists
Estradiol
Cannabinoid Receptor CB1
Cannabinoid Receptors
Menstrual Cycle
Lipase
Transgenic Mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ghrelin Decreases Firing Activity of Gonadotropin-Releasing Hormone (GnRH) Neurons in an Estrous Cycle and Endocannabinoid Signaling Dependent Manner. / Farkas, Imre; Vastagh, Csaba; Sárvári, Miklós; Liposits, Z.

In: PLoS One, Vol. 8, No. 10, e78178, 04.10.2013.

Research output: Article

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