INVESTIGADORES
CISTERNAS carla Daniela
artículos
Título:
DNA methylation and demethylation underlie the sex difference in estrogen receptor alpha in the arcuate nucleus
Autor/es:
CORTES, LAURA R; CISTERNAS CARLA DANIELA; CABAHUG IAGN N K V ; MASON DAMIAN; RAMLALL EMMA K ; CASTILLO-RUIZ ALEXANDRA; FORGER NANCY G
Revista:
NEUROENDOCRINOLOGY
Editorial:
KARGER
Referencias:
Lugar: Basel; Año: 2021
ISSN:
0028-3835
Resumen:
Introduction: Neurons expressing estrogen receptor (ER) ɑ in the arcuate (ARC) and ventromedial (VMH) nuclei of the hypothalamus sex-specifically control energy homeostasis, sexual behavior, and bone density. Females have more ERalpha neurons in the VMH and ARC compared to males, and the sex difference in the VMH is eliminated by neonatal treatment with testosterone or a DNA methylation inhibitor. Objective: Here, we tested the roles of testosterone and DNA methylation/demethylation in development of ERalpha in the ARC. Methods: ERalpha was examined at birth and weaning in mice that received vehicle or testosterone subcutaneously, and vehicle or a DNA methyltransferase inhibitor intracerebroventricularly, as neonates. To examine effects of DNA demethylation on ERalpha cell number in the ARC, mice were treated neonatally with small interfering RNAs against ten-eleven translocase enzymes. Methylation status of the ERalpha gene (Esr1) was determined in the ARC and VMH using pyrosequencing of bisulfite-converted DNA. Results: A sex difference in ERalpha in the ARC, favoring females, developed between birth and weaning and was due to programming effects of testosterone. Neonatal inhibition of DNA methylation decreased ERɑ in the ARC of females, and an inhibition of demethylation increased ERalpha in the ARC of males. The promoter region of Esr1 exhibited a small sex difference in percent of total methylation in the ARC (females > males) that was opposite to that in the VMH (males > females). Conclusion: DNA methylation and demethylation regulate ERalpha cell number in the ARC, and methylation correlates with activation of Esr1 in this region.