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

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.

Participation of TRPV1 in the activity of the GnRH system in male rats

“…changing RFRP3 levels (Iwasa et al, 2015;Lee et al, 2019). Moreover, it has been reported that an icv administration of RFRP3 does not affect Gnrh or Kiss1 expression (Lee et al, 2019). In our study, we found that a high dose of LPS increased Rfrp3 levels and decreased Gnrh and Kiss1 levels, although we cannot discern if RFRP3 directly participates in the inhibition of the stimulatory neuropeptides.…”

“…changing RFRP3 levels (Iwasa et al, 2015;Lee et al, 2019). Moreover, it has been reported that an icv administration of RFRP3 does not affect Gnrh or Kiss1 expression (Lee et al, 2019).…”

“…The role of RFRP3 on GnRH synthesis has been under revision during the last years. On the one hand, it has been reported that a high dose of LPS (5mg/kg) is needed to increase RFRP3 levels and concomitantly decrease GnRH levels (Iwasa et al., 2014), but, on the other hand, it seems that lower doses of LPS can also inhibit GnRH levels without changing RFRP3 levels (Iwasa et al., 2015; Lee et al., 2019). Moreover, it has been reported that an icv administration of RFRP3 does not affect Gnrh or Kiss1 expression (Lee et al., 2019).…”

Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences

“…Recent data presented that the kisspeptin system is sensitive to inflammation. Systemic endotoxin injection (LPS) in female rat decreases KISS-1 mRNA expression in the hypothalamus that consequently suppresses LH [91,92]. Moreover, intravenous (i.v.)…”

“…Inflammation may inhibit GnRH secretion via alteration of the RFRP system as LPS injection has been demonstrated to elevate hypothalamic RFRP and GPR147 mRNA levels in rodents [91,92]. Since RFRPs modulate kisspeptin signaling, inflammation might also have an effect on GnRH pulse generation via the RFRP system.…”