摘要
Objective:Female reproductive aging is characterized by reduced responsiveness of the hypothalamus to E2-positive feedback,which can result in alterations of gene expression and luteinizing hormone(LH)surge dysfunction.We hypothesize that age-related changes in E2-responsive gene expression are due to altered histone acetylation by histone deacetylases(HDACs)or estrogen receptor-alpha(ERα)coactivators with histone acetyltransferase(HAT)activity.Methods:In the present study,young and middle-aged female rats were ovariectomized(OVX)and treated with E2 or oil once per day for 2 days.At the time of the expected LH surge,the anterior and posterior hypothalami were dissected,and gene expression of 11 HDACs and 4 ERαcoactivators with HAT activity was measured using real-time polymerase chain reaction.Results:In the anterior hypothalamus,age affected the gene expression of 3 HDACs(Hdac3,Hdac5,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp).E2 treatment significantly decreased mRNA levels of 4 HDACs(Hdac4,Hdac5,Hdac10,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp)in young females(3-4 months).However,none of the genes responded to E2 in the middle-aged females(9-11 months),except Hdac10.In the posterior hypothalamus,age influenced Hdac5 and Src1 mRNA expression.E2 treatment increased Hdac4 and Crebbp mRNA levels in the young but not middle-aged females.Conclusions:These data suggest that E2 regulates HDACs and ERαcoactivators with HAT activity in an age-and E2-dependent manner,which may contribute to the age-related gene expression changes on the day of LH surge in female reproductive aging.
基金
funded by Shanghai Science and Technology Committee(17ZR1403300).
