Reas (Granata et al., 2014; Pr ost et al., 2015). IKKε site within the human adrenal gland, the QRFP receptor is exclusively expressed during embryogenesis within the fetal zone but not inside the zona glomerulosa or adrenal medulla, whereas inside the adult human adrenal gland, QRFP receptor mRNA is present in all three zones from the cortex. Inside the rat adrenal gland, the medulla is devoid of QRFP receptor mRNA (Ramanjaneya et al., 2013).British Journal of Pharmacology (2017) 174 3573607BJPJ Leprince et al.QRFP receptor knockoutSo far, only QRFP receptor 1 knockout animals have been reported within the literature. QRFP receptor 1 knockout mice on a C57Bl6/J background endure from kyphosis and display osteopenia (Baribault et al., 2006). This phenotype is extra frequent in females than males (80 vs. 10 respectively) and is enhanced by ovariectomy. Detailed analysis using microcomputed tomography reveals a decrease in trabecular bone density inside the spine in each sexes. The reduction in bone density is extra pronounced in female than male knockout mice having a ERK2 list thinning with the osteochondral development plate. In contrast, no evidence for calcium, phosphate, vitamin D or parathyroid hormone changes may be detected in the knockout mice. Regardless of this phenotype, knockout mice seem to develop typically and no difference in body weight was reported (Baribault et al., 2006). Interestingly, SAMP6 osteopenic mice display a singlenucleotide polymorphism (SNP) in the promoter region and three SNPs, such as one particular silent SNP, in the coding area with the QRFP prepropeptide, upstream the sequence of QRFP (Zhang et al., 2007). In these mice, QRFP expression is reduced within the lumbar spine and within the hypothalamus, suggesting that the SNP in the promoter area of the gene final results in generation of a putative repressive transcription issue binding web site (Zhang et al., 2007). In human, 3 SNPs within the QRFP receptor gene show significant association with Hashimoto’s thyroiditis within the Japanese (Ban et al., 2016) and Caucasian (Tomer et al., 2015) populations.QRFP receptors in tumour cellsQRFP receptor transcript is detected in the androgenunresponsive prostate cancer cell line DU145 but not within the androgen-unresponsive PC3 cell line and in the androgenresponsive LNCaP cell line (Alonzeau et al., 2013). The human adrenal corticocarcinoma cell line H295R also expresses QRFP receptor mRNA (Ramanjaneya et al., 2013).Biological and pharmacological effects of QFRP peptidesEffects of QRFP peptides on the CNSCentral regulation of feeding behaviour by QRFP peptides. The observation that the QRFP precursor is mainly expressed in hypothalamic nuclei involved within the handle of energy homeostasis, like the ARC, PVN, VMH and LHyp (Chartrel et al., 2003; Fukusumi et al., 2003; Bruzzone et al., 2006; Kampe et al., 2006; Takayasu et al., 2006), has led researchers to investigate the achievable effect of 26RFa/QRFP on meals intake. The earliest report on the action of 26RFa/QRFP on feeding behaviour revealed that i.c.v. administration of 26RFa in food-restricted mice causes a dose-dependent increase in chow consumption (Chartrel et al., 2003). Quite a few research have supported this initial observation and expanded the original findings by investigating the effects of 26RFa/QRFP on food intake in totally satiated mice and following chronic administration of 26RFa/QRFP (Do Rego et al., 2006; Moriya et al., 2006; Takayasu et al., 2006). Notably, chronic administration of3596 British Journal of Pharmacology (2017) 174.
