Expression and methylation status of female-predominant GH-dependent liver genes are modified by neonatal androgenization in female mice

RAMIREZ,M.C.; ZUBELDIA BRENNER, L.; WARGON,V.; ORNSTEIN AM; BECU VILLALOBOS, DAMASIA

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2014 vol. 382 p. 825 - 835

0303-7207

Neonatal androgenization masculinizes the GH axis and thus may impact on liver gene regulation. Neonatal testosterone administration to female mice decreased (defeminized) female predominant GH-dependent liver gene expression (Hnf6Adh1PrlrCyp3a41) and did not modify male predominant genes(Cyp7b1Cyp4a12Slp). Female predominance of Cis mRNA, an inhibitor of episodic GH signaling pathway,was unaltered. At birth,Cyp7b1promoter exhibited a higher methylation status in female livers, while theHnf6 promoter was equally methylated in both sexes; no differences in gene expression were detected atthis age. In adulthood, consistent with sex specific predominance, lower methylation status was deter- mined for theCyp7b1promoter in males, and for theHnf6promoter in females, and this last differencewas prevented by neonatal androgenization. Therefore, early steroid treatment or eventually endocrinedisruptor exposure may alter methylation status and sexual dimorphic expression of liver genes, and consequently modify liver physiology in females.