Growth hormone-releasing hormone: Not only a neurohormone

ArticleinTrends in Endocrinology and Metabolism 22(8):311-7 · April 2011with4 Reads
DOI: 10.1016/j.tem.2011.03.006 · Source: PubMed
Growth hormone-releasing hormone (GHRH) is mostly thought to act by stimulating the production and release of growth hormone from the pituitary. However, this neuropeptide emerges as a rather pleiotropic hormone in view of the identification of various extrapituitary sources for GHRH production, as well as the demonstration of a direct action of GHRH on several tissues other than the pituitary. Non-pituitary GHRH has a wide spectrum of activity, exemplified by its ability to modulate cell proliferation, especially in malignant tissues, to regulate differentiation of some cell types, and to promote healing of skin wounds. These findings extend the role of GHRH and its analogs beyond its accepted regulation of somatotropic activity and indicate new possibilities for therapeutic intervention.
    • "GHRH may also play a role in the activation of stromal fibroblasts in the tumor microenvironment by regulating í µí»¼-SMA expression. It remains to be elucidated whether GHRH specifically affects GSCs and its effects on tumor endothelial cells [120]. [11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Malignant gliomas are aggressive brain tumors with limited therapeutic options, possibly because of highly tumorigenic subpopulations of glioma stem cells. These cells require specific microenvironments to maintain their “stemness,” described as perivascular and hypoxic niches. Each of those niches induces particular signatures in glioma stem cells (e.g., activation of Notch signaling, secretion of VEGF, bFGF, SDF1 for the vascular niche, activation of HIF2 α , and metabolic reprogramming for hypoxic niche). Recently, accumulated knowledge on tumor-associated macrophages, possibly delineating a third niche, has underlined the role of immune cells in glioma progression, via specific chemoattractant factors and cytokines, such as macrophage-colony stimulation factor (M-CSF). The local or myeloid origin of this new component of glioma stem cells niche is yet to be determined. Such niches are being increasingly recognized as key regulators involved in multiple stages of disease progression, therapy resistance, immune-escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. This review focuses on the microenvironment impact on the glioma stem cell biology, emphasizing GSCs cross talk with hypoxic, perivascular, and immune niches and their potential use as targeted therapy.
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    • "GHRH is a proteinnencoding gene, which encodes protein GHRH. The main function of GHRH is conn sidered to be regulation of GH production and release [43]. The other functions of GHRH include acceleraa tion of wound healing [44], protecting cardiomyocytes from apoptosis [45], promoting of proliferation and survival of the pancreatic islet cells [46], and regulaa tion of cellular functions not only in tumor biology but also in other processes [47][48][49]. "
    [Show abstract] [Hide abstract] ABSTRACT: Umbilical hernia (UH) is a complex disorder caused by both genetic and environmental factors. UH brings animal welfare problems and severe economic loss to the pig industry. Until now, the genetic basis of UH is poorly understood. The high-density 60K porcine SNP array enables the rapid application of genome-wide association study (GWAS) to identify genetic loci for phenotypic traits at genome wide scale in pigs. The objective of this research was to identify susceptibility loci for swine umbilical hernia using the GWAS approach. We genotyped 478 piglets from 142 families representing three Western commercial breeds with the Illumina PorcineSNP60 BeadChip. Then significant SNPs were detected by GWAS using ROADTRIPS (Robust Association-Detection Test for Related Individuals with Population Substructure)software base on a Bonferroni corrected threshold (P = 1.67E-06) or suggestive threshold (P = 3.34E-05) and false discovery rate (FDR = 0.05). After quality control, 29924 qualified SNPs and 472 piglets were used for GWAS. Two suggestive loci predisposing to pig UH were identified at 44.25MB on SSC2 (rs81358018, P = 3.34E-06, FDR = 0.049933) and at 45.90MB on SSC17 (rs81479278, P = 3.30E-06, FDR = 0.049933) in Duroc population, respectively. And no SNP was detected to be associated with pig UH at significant level in neither Landrace nor Large White population. Furthermore, we carried out a meta-analysis in the combined purebreed population containing all the 472 piglets. rs81479278 (P = 1.16E-06, FDR = 0.022475) was identified to associate with pig UH at genome-wide significant level. SRC was characterized as plausible candidate gene for susceptibility to pig UH according to its genomic position and biological functions. To our knowledge, this study gives the first description of GWAS identifying susceptibility loci for umbilical hernia in pigs. Our findings provide deeper insights to the genetic architecture of umbilical hernia in pigs.
    Full-text · Article · Oct 2015
    X. J. LiaoX. J. LiaoL. LiL. LiZ. Y. ZhangZ. Y. Zhang+1more author...[...]
    • "We then looked for other causes of impaired fissure healing. Since there is evidence in the literature that growth hormones play an important role in wound healing [26, 27] , we looked for endocrine causes. A computed tomography scan of the brain showed an empty sella, a rather common incidental finding, which may be associated with hypopituitarism of varying degrees [28]. "
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