The Type 2 Corticotrophin‐Releasing Hormone Receptor Mediates Orexin A‐Induced Luteinising Hormone Suppression in Ovariectomised Rats

Iwasa, Takeshi; Matsuzaki, Takashi; Kiyokawa, Machiko; Shimizu, Fumi; Minakuchi, Masahiro; Kuwahara, Akira; Murakami, Masahiko; Irahara, Minoru

doi:10.1111/j.1365-2826.2007.01583.x

Cited by 24 publications

(30 citation statements)

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“…Orexin, which has crucial role in the sleep–wakefulness cycle and appetite control, affects GnRH1 release directly or via the NPY-, CRH-, and β-endorphin-signaling pathways (Li et al, 1999; Tamura et al, 1999; Irahara et al, 2001; Yang et al, 2005; Iwasa et al, 2007). In goldfish, ICV administration of orexin A suppresses spawning behavior, and ICV administration of GnRH2 reduces the level of orexin precursor mRNA in the brain (Hoskins et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

Nishiguchi¹,

Azuma²,

Yokobori³

et al. 2012

Front. Endocrin.

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Gonadotropin-releasing hormone (GnRH) is an evolutionarily conserved neuropeptide with 10 amino acid residues, of which several structural variants exist. A molecular form known as GnRH2 ([His5 Trp7 Tyr8]GnRH, also known as chicken GnRH II) is widely distributed in vertebrates except for rodents, and has recently been implicated in the regulation of feeding behavior in goldfish. However, the influence of GnRH2 on feeding behavior in other fish has not yet been studied. In the present study, therefore, we investigated the role of GnRH2 in the regulation of feeding behavior in a zebrafish model, and examined its involvement in food intake after intracerebroventricular (ICV) administration. ICV injection of GnRH2 at 0.1 and 1 pmol/g body weight (BW) induced a marked decrease of food consumption in a dose-dependent manner during 30 min after feeding. Cumulative food intake was significantly decreased by ICV injection of GnRH2 at 1 pmol/g BW during the 30-min post-treatment observation period. The anorexigenic action of GnRH2 was completely blocked by treatment with the GnRH type I receptor antagonist Antide at 25 pmol/g BW. We also examined the effect of feeding condition on the expression level of the GnRH2 transcript in the hypothalamus. Levels of GnRH2 mRNA obtained from fish that had been provided excess food for 7 days were higher than those in fish that had been fed normally. These results suggest that, in zebrafish, GnRH2 acts as an anorexigenic factor, as is the case in goldfish.

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Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

Nishiguchi¹,

Azuma²,

Yokobori³

et al. 2012

Front. Endocrin.

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“…injections of GnRH inhibiting factors such as hypocretin (HCRT; also known as orexin) and 2-buten-4-olide suppressed plasma LH levels immediately after injection, with the suppression being sustained for at least 1 h (Saito et al 1993, Kaji et al 1998, Tamura et al 1999, Iwasa et al 2007). Kriegsfeld et al (2006) deduced that RFRP-3 suppresses LH secretion at the hypothalamic level, as more than 40% of the GnRH neurons were projected from the GnIH-immunoreactive fibers.…”

Section: Discussionmentioning

confidence: 99%

Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats

Murakami¹,

Matsuzaki²,

Iwasa³

et al. 2008

Journal of Endocrinology

222

174

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Gonadotropin-inhibitory hormone (GnIH), a newly discovered hypothalamic RFamide peptide, inhibits reproductive activity by decreasing gonadotropin synthesis and release in birds. The gene of the mammalian RFamide-related peptides (RFRP) is orthologous to the GnIH gene. This Rfrp gene gives rise to the two biologically active peptides RFRP-1 (NPSF) and RFRP-3 (NPVF), and i.c.v. injections of RFRP-3 suppress LH secretion in several mammalian species. In this study, we show whether RFRP-3 affects LH secretion at the pituitary level and/or via the release of GnRH at the hypothalamus in mammals. To investigate the suppressive effects of RFRP-3 on the mean level of LH secretion and the frequency of pulsatile LH secretion in vivo, ovariectomized (OVX) mature rats were administered RFRP-3 using either i.c.v. or i.v. injections. Furthermore, the effect of RFRP-3 on LH secretion was also investigated using cultured female rat pituitary cells. With i.v. administrations, RFRP-3 significantly reduced plasma LH concentrations when compared with the physiological saline group. However, after i.c.v. RFRP-3 injections, neither the mean level of LH concentrations nor the frequency of the pulsatile LH secretion was affected. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 on LH secretion was not clear, but when GnRH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that RFRP-3 does not affect LH secretion via the release of GnRH, and that RFRP-3 directly acts upon the pituitary to suppress GnRH-stimulated LH secretion in female rats.

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“…Our group and others have found that the expression levels of kisspeptin and its receptor, which are positive regulators of GnRH, are also sensitive to immune stress (Watanobe and Hayakawa, 2003; Kisney‐Jones et al, 2009). We reported that high dose LPS injection suppressed hypothalamic Kiss1, Kiss1r , and GnRH mRNA expression in female rats (Iwasa et al, 2007; Iwasa et al, 2014). However, the expression levels of these molecules were not affected by the injection of a lower dose of LPS at any examined age in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…This indicates that the HPG axis acquires sensitivity to immune stress around PND25 in rats, which is similar to the age at which the HPA axis becomes sensitive to immune stress (Witek‐Janusek, 1988; Spencer et al, 2006 ). In adulthood, immune stress activates HPA axis (Shanks et al, 1995; Ellis et al, 2006) and induces hypothalamic CRH mRNA expression, which suppresses LH secretion mediated by CRH‐R2 on GnRH neuron (Li et al, 2005, 2006; Iwasa et al, 2007, 2009). Suppressed LH secretion at PND 25 might be related to HPA axis that acquire sensitivity to LPS at PND 21 (Witek‐Janusek, 1988).…”

Section: Discussionmentioning

confidence: 99%

The suppressive effect of immune stress on LH secretion is absent in the early neonatal period in rats

Munkhzaya

Matsuzaki

Iwasa

et al. 2015

Intl J of Devlp Neuroscience

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Some physiological functions display weak responses to stress in the early neonatal period; i.e., they exhibit stress hyporesponse periods. In this study, we evaluated whether gonadotropin regulatory factors exhibit stress hyporesponsive periods in male and female rats. Rats were intraperitoneally injected with lipopolysaccharide (100μg/kg) (LPS group) or saline (control group) on postnatal day (PND) 5, 10, 15, or 25. Then, their serum luteinizing hormone (LH) concentrations and hypothalamic mRNA levels of gonadotropin regulatory factors; i.e., kisspeptin (Kiss1), the kisspeptin receptor (Kiss1r), and gonadotropin-releasing hormone (GnRH), were measured at 2h after the injection. The hypothalamic mRNA levels of pro-inflammatory cytokines were also measured because they suppress gonadotropin secretion. The serum LH concentration of the LPS group was lower than that of the control group at PND25 in both sexes, but no such difference was seen at PND5, 10, or 15 in either sex. In both sexes, the hypothalamic tumor necrosis factor (TNF)α and interleukin (IL)-6 mRNA expression levels of the LPS group were higher than those of the control group at PND25, but not at PND5 or 10. The hypothalamic IL-1β mRNA expression level of the LPS group was higher than that of the control group at all time points. The hypothalamic Kiss1, Kiss1r, and GnRH mRNA expression levels of the LPS and control groups did not differ at any time point in either sex. These findings suggest that gonadotropin regulatory factors exhibit stress hyporesponse periods. The hypothalamic-pituitary-gonadal axis (HPG) might become responsive to immune stress between PND15 and 25, which could be related to enhanced hypothalamic cytokine expression. The avoidance of infectious stress during the early neonatal period might be important for normal development of the HPG axis.

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The Type 2 Corticotrophin‐Releasing Hormone Receptor Mediates Orexin A‐Induced Luteinising Hormone Suppression in Ovariectomised Rats

Cited by 24 publications

References 50 publications

Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats

The suppressive effect of immune stress on LH secretion is absent in the early neonatal period in rats

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