IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Growth hormone induced epigenetic changes in liver sexually dimorphic gene expression
Autor/es:
RAMIREZ, MARIA CECILIA ; BRIE, BELEN; BECU-VILLALOBOS, DAMASIA; ORNSTEIN, ANA MARIA; DE WINNE, CATALINA
Reunión:
Congreso; Reunión Anual SAIC-SAI-SAFE; 2016
Resumen:
Growth hormone (GH) secretion is sexually dimorphic in many species, such as rodents and humans. In the liver GH regulates gene expression in a sexual dimorphic manner. Previous results from our laboratory showed that central disruption of the Dopamine D2 Receptor (D2R) altered the growth axis, we thus inferred and searched for alterations of sexually dependent liver gene expression. To this end, we used transgenic mice with the D2R depleted from the nervous system (neuroDrd2KO). Furthermore, because neonatal sexual steroids are known to imprint the growth axis, we tested the effects of the neonatal administration of testosterone in females on genetic and epigenetic regulation of the liver. We sustained that liver sexual dimorphism is mediated by epigenetic mechanisms, induced by the GH secretion pattern. Hypermethylation of promoter regions of genes generally results in their silencing. We measured promoter methylation levels using a methylation sensitive restriction enzyme, followed by specific qPCR. We found that the mRNA expression of female predominant genes Alcohol Dehydrogenase 1 (Adh1) and Hepatocyte Nuclear Factor 6 (Hnf-6) are masculinized in the neuroDrd2KO mice, and so was the Adh1 protein. On the other hand, mRNA expression of the male predominant gene Cyp7b1 was feminized (decreased) in both our mice models. Increased methylation of the promoter region of Hnf-6 correlated with its decreased expression in neuroDrd2KO females, while increased expression of Adh1 in neuroDrd2KO males did not correlate with methylation status of its promoter. Furthermore, methylation could not explain the changes in Cyp7b1 in neuroDrd2KO mice. Lastly Adh1 and Hnf6 mRNA in the testosterone treated females was masculinized and altered methylation of the promoter correlated only with Hnf6 expression.Our results demonstrate that the growth axis modulates the sexual dimorphic expression of several genes in the liver, in part through DNA methylation.