Dimorfismo sexual del hígado dependiente de GH y prolactina : impacto sobre el metabolismo
Growth hormone (GH) release pattern, which shows prominent sexual differences, impacts the sexual dimorphic expression of multiple liver genes, and liver pathologies related to sex have been described, including non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma.\nWe found that epigen...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6407 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6407.dir/6407.PDF |
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| Sumario: | Growth hormone (GH) release pattern, which shows prominent sexual differences, impacts the sexual dimorphic expression of multiple liver genes, and liver pathologies related to sex have been described, including non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma.\nWe found that epigenetic mechanisms participate in the sexually dimorphic gene expression and that the regulation by GH, but not prolactin of Cyp7b1, Cyp2a4, Hnf6 and Prlr genes can be achieved through promoter methylation or microRNAs. Moreover, we found that alterations in the liver GHR, STAT5b, liver IGF1, and serum GH levels, modify the sexual dimorphism of several liver genes such as Hao2, Hamp, Lcn13, Asns, Cyp2b9, Cyp7b1, and Pgc1a in the liver. Modifications found were specific to each gene and sex, and point to a sophisticated array of gene liver regulation which depends on GH signaling.\nOn the other hand, we observed the possibility of a correlation between physiology and hepatic sexual dimorphism. Sexually dimorphic enzyme ADH1 could participate in the differential consumption and preference of ethanol between sexes. Likewise, the different susceptibility to liver pathologies, like NASH, could be mediated by hepatic GH signaling, which impacts on sexually dimorphic gene expression in the liver, and an appropriate dimorphism is necessary for proper liver metabolism. |
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