Mechanism of appetite regulating peptides

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1, Regulation of the human ghrelin promoter activityTo examine the gene expression of ghrelin, a growth hormone-releasing and appetite-stimulating hormone produced by the stomach, we constructed human ghrelin promoter-reporter vectors and analyzed promoter activity. Ghrelin promoter activity was high in cultured cells that endogenously express ghrelin mRNA, such as TT or ECC10 cells, indicating that these cells contain the factors necessary for full expression of human ghrelin. The human ghrelin promoter contains both positive and negative regulatory elements. A transient decrease in promoter activity was observed following transfection of a reporter vector containing the -1600 fragment of the human ghrelin promoter into cultured cells. We examined the effect of several transcription factors on ghrelin promoter activity ; NF-kB suppressed, while Nkx2.2, a homeodomain-containing transcription factor important for ghrelin-producing cell development in the pancreas, activates promoter activity. Lipopolysaccharide (LPS) binds Toll-like receptor 4, whose downstream signaling activates NF-kB. As LPS suppresses ghrelin expression levels, LPS may suppress ghrelin gene expression by activating NF-kB.2, Regulation of gonadotropin secretion and puberty onset by neuromedin UNeuromedin U (NMU), an anorexigenic peptide, was originally isolated from porcine spinal cord in 1985. As NMU is abundant in the anterior pituitary gland, we investigated the effects of NMU on gonadotropin secretion. Both NMU and its receptors, NMUR1 and NMUR2, were expressed in the pituitary gland. NMU suppressed LH and FSH releases from rat anterior pituitary cells. Moreover, NMU-deficient mice exhibit an early onset of vaginal opening. The LHbeta/FSHbeta ratio, which is an index of puberty onset, is high in young NMU-deficient mice. These results indicate that NMU suppresses gonadotropin secretion and regulates the onset of puberty.