Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin

Lee CY 1 , Li S 2 , Li XF 2 , Stalker DAE 3 , Cooke C 2 , Shao B 4 Show all authors , Kelestimur H 5 , Henry BA 6 , Conductier G 3 , O Byrne KT 2 , Clarke IJ 7

Affiliations 

  • 1 School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Subang Jaya, Selangor, Malaysia
  • 2 Division of Women's Health, Women's Health Academic Centre, Faculty of Life Sciences and Medicine, King's College London, Guy's Campus, London, WC2R 2LS, UK
  • 3 Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Vic. 3800, Australia
  • 4 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325003, China
  • 5 Department of Physiology, Faculty of Medicine, Firat University, Elazig, 90424, Turkey
  • 6 Metabolism, Diabetes and Obesity Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Vic. 3800, Australia
  • 7 Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Vic. 3800, Australia; and Corresponding author. Email: iain.clarke@monash.edu
Reprod Fertil Dev, 2019 May;31(6):1134-1143.
PMID: 30922440 DOI: 10.1071/RD18277

Abstract

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15μgkg-1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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