Expression and methylation status of female-predominant GH-dependent liver genes are modified by neonatal androgenization in female mice.
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 (Hnf6, Adh1, Prlr, Cyp3a41) and did not modify male predominant genes (Cyp7b1, Cyp4a12, Slp). Female predominance of Cis mRNA, an inhibitor of episodic GH signaling pathway, was unaltered. At birth, Cyp7b1 promoter exhibited a higher methylation status in female livers, while the Hnf6 promoter was equally methylated in both sexes; no differences in gene expression were detected at this age. In adulthood, consistent with sex specific predominance, lower methylation status was determined for the Cyp7b1 promoter in males, and for the Hnf6 promoter in females, and this last difference was prevented by neonatal androgenization. Therefore, early steroid treatment or eventually endocrine disruptor exposure may alter methylation status and sexual dimorphic expression of liver genes, and consequently modify liver physiology in females.
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina.
Maria Cecilia
MC
Ramirez
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina.
Lautaro
L
Zubeldía-Brenner
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina.
Victoria
V
Wargon
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina.
Ana María
AM
Ornstein
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina. Electronic address: dbecu@dna.uba.ar.
Damasia
D
Becu-Villalobos
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000072474:Cytochrome P450 Family 7; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012727:Sex Characteristics; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D014770:Virilism / Q000235:genetics
D000728:Androgens; D051559:Hepatocyte Nuclear Factor 6; C496606:Onecut1 protein, mouse; D013739:Testosterone; D013006:Growth Hormone; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C097207:Cyp7b1 protein, mouse
Cyps; DNA methylation; GH; Liver; Neonatal testosterone; Sexual differences