雌孕激素治疗对绝经后代谢综合征患者雌雄激素受体基因表观遗传调控的影响

Effects of menopausal hormone therapy on epigenetic regulation of estrogen/androgen receptor genes in postmenopausal patients with metabolic syndrome

目的观察绝经早期妇女应用雌孕激素治疗(MHT)对雌、雄激素受体(ER、AR)基因的表观遗传调控,探索绝经后性激素变化及绝经激素治疗与代谢综合征(MS)之间的相关性及其可能的作用机制。方法检测绝经早期妇女性激素水平及ER、AR基因甲基化状态,评估MS及其各组分组上述指标的差异,以及MHT6~12个月后各组ER、AR基因甲基化修饰的变化特点及组间差异。结果①低E2/T比值与绝经1~5年妇女高血压及高血糖有关。②入组时MS及其各组分异常者与其ER、AR基因甲基化状态及甲基化程度未发现相关;但MHT6个月可对非MS组及高血压组的ER基因产生去甲基化作用,且作用可持续至治疗12个月时;MHT对MS及高血脂者ER基因也可产生去甲基化作用,但该作用在MHT12个月时方才显现。③MHT对AR基因甲基化修饰的作用不明显,除治疗12个月时对腰围异常者AR基因有促进甲基化作用外,对其余各组均未见明显的影响。结论MHT6~12个月可对大部分绝经早期女性ER基因进行去甲基化修饰,而对AR基因甲基化状态无显著影响。

Objective To observe the epigenetic regulation of estrogen and androgen receptor genes(ER and AR)in early menopausal women by using estrogen and progesterone therapy(MHT),and to explore the correlation between postmenopausal sex hormone changes,menopausal hormone therapy and metabolic syndrome(MS)and its possible mechanism.Methods The sex hormone level and the methylation status of ER and AR genes in early menopausal women were detected,and the differences of the above indicators in MS and each component parts group were evaluated,as well as the changes of ER and AR gene methylation modification characteristics and the differences between groups after MHT 6-12 months.Results(1)Low E2/T ratio was associated with hypertension and hyperglycemia in postmenopausal women.(2)There was no correlation between the methylation status and methylation degree of ER and AR genes of MS and its different components groups.However,MHT 6 months could exert demethylation effect on ER gene of non-MS group and hypertension group,and the effect lasted for 12 months.MHT could also exert demethylation effect on the ER gene of MS and hyperlipidemia group,but this effect was not apparent until MHT 12 months.(3)MHT had no significant effect on the methylation of AR gene.Except for the effect of promoting methylation level of AR gene in the patients with abnormal waist circumference at 12 months after treatment,there was no significant effect for the other groups.Conclusion MHT for 6-12 months can demethylate the ER gene of most early menopausal women,but has no significant effect on the methylation status of AR gene.