Middle-aged female rats lack changes in histone H3 acetylation in the anterior hypothalamus observed in young females on the day of a luteinizing hormone surge.

Histone acetylation has recently been implicated in gene transcription and estradiol (E2) actions in the hypothalamus. This study aims to determine the involvement of histone acetylation in mediating E2-induced luteinizing hormone (LH) surge to understand the mechanism underlying LH surge dysfunction in female reproductive aging. Young and middle-aged female rats were ovariectomized (OVX) and treated with hormone or oil once per day for two days. At the time of the expected LH surge, blood samples were taken for LH assay. The anterior and posterior hypothalami were dissected, histone H3/H4 acetylation and histone deacetylases (HDACs) 4, -5, -10 and -11 protein expressions were measured using Western blotting. Our results show that in the young females, E2 markedly increased histone H3 acetylation while significantly reducing HDAC10 protein expression in the anterior hypothalamus. Notably, E2-induced alterations of histone H3 acetylation and HDAC10 in the anterior hypothalamus were absent in middle-aged females, associated with a reduced LH release. However, age alters histone H4 acetylation in both the anterior and posterior hypothalamus and significantly increased HDAC 4 and -5 protein expression in the anterior hypothalamus. Taken together, these data suggest that histone H3 acetylation in the anterior hypothalamus may mediate E2 regulation of LH surge and the process possibly through decreasing HDAC10. The missed responsiveness of histone H3 acetylation and HDAC10 expression to E2 in the anterior hypothalamus may contribute to LH surge failure that occurs in female reproductive aging.