Effects And Its Mechanisms Of BHBA On GHRH Expression And Secretion In Rat Hypothalamus

Growth and development of mammals is regulated by a complex series ofregulation system, which originated in the hypothalamus. GHRH and SST are twoimportant peptides for pituitary cells, which are secreted by the hypothalamus. GHRHpromotes the secretion of GH on the pituitary gland, and than it can increase theproduction of IGF-1in the liver and other tissues. GH promotes the body’smetabolism in the form of IGF-1in the liver.As an important intermediate product of fatty acid metabolism,β-hydroxybutyricacid (BHBA) is similar to glucose in that it can be used by the brain to provide energy,particularly for suckling newborns. In recent years, studies have shown that BHBA canregulate the synthesis and secretion of hormones in the hypothalamus. However, themechanism of synthesis and secretion of BHBA mediated regulation of hormone orCHRH is seldom reported. Studies have shown BHBA can inhibit LPS-inducedinflammation by GPR109A. Studies have also shown that BHBA can promotesadiponectin secretion by GPR109A.In our previous studies, we found there are the expression of GPR109A which isthe receptor of BHBA in primary cultured hypothalamic cells. Therefore, we assumethat BHBA can regulate the synthesis and secretion of GHRH through GPR109A andits downstream. BHBA significantly reduced the transcription of GHRH in vivo in ourexperiments. In vitro, experiments showed BHBA reduced synthesis and secretion ofGHRH in primary cultured hypothalamic cells, but when pretreated with PTX, theeffect was blocked. In GT1-7cell line, there was no effect, but when transfected byGPR109A,the synthesis and secretion of GHRH was nificantly suppressed,and thiseffect could be blocked by PTX. In addition, BHBA can significantly reduce thetranscription of Gsh-1, and PTX can also block this effect. The results of westernblotting have showed BHBA can activate ERK1/2, p38and JNK MAPK signalingpathway in primary cultured hypothalamic cells. Moreover, U0126can inhibit ERK1/2signaling pathways to make the effect that BHBA inhibited expression of Gsh-1and synthesis and secretion of GHRH weakened. These results showed that the BHBA candown regulate the expression of Gsh-1and synthesis and secretion of GHRH quicklythrough the GPR109A/ERK1/2MAPK pathway.