LAUSR

Significance The arcuate nucleus (ARC) of the mediobasal hypothalamus is critically involved in hormonal communication from ovary to brain. Negative estrogen feedback to kisspeptin synthesizing neurons of the ARC is a crucial determinant of hypothalamic gonadotropin-releasing hormone secretion regulating fertility. We performed deep transcriptome profiling of ARC kisspeptin neurons with RNA sequencing and identified over 2,000 estrogen-sensitive transcripts. Several genes responding to estrogen treatment in ovariectomized mice exhibited rare variants in a patient database with pubertal defects and emerge as candidate genes for a role in puberty/fertility disorders. Comprehensive characterization of the estrogen-dependent kisspeptin neuron transcriptome in mice has important clinical implications for the hypothalamic regulation of human menstrual cycle and for the putative molecular consequences of postmenopausal estrogen deficiency.