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RESEARCH ARTICLE

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

Chooi Yeng Lee A , ShengYun Li B , Xiao Feng Li B , Daniel A. E. Stalker C , Claire Cooke B , Bei Shao D , Haluk Kelestimur E , Belinda A. Henry F , Gregory Conductier C , Kevin T. O’Byrne B and Iain J. Clarke https://orcid.org/0000-0002-6613-2757 C G
+ Author Affiliations
- Author Affiliations

A School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Subang Jaya, Selangor, Malaysia.

B 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.

C Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Vic. 3800, Australia.

D Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325003, China.

E Department of Physiology, Faculty of Medicine, Firat University, Elazig, 90424, Turkey.

F Metabolism, Diabetes and Obesity Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Vic. 3800, Australia.

G Corresponding author. Email: iain.clarke@monash.edu

Reproduction, Fertility and Development 31(6) 1134-1143 https://doi.org/10.1071/RD18277
Submitted: 18 July 2018  Accepted: 29 January 2019   Published: 29 March 2019

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 (15 μg kg−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.

Additional keywords: hypothalamus, neuroendocrinology, neuropeptides, stress.


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