UC San Diego

In females, estrogen signaling is necessary for coordinating ovulation and the menstrual cycle. KISS1, a gene expressed by kisspeptin neurons and critical for reproduction, is positively and negatively regulated by 17β-estradiol (E2), an endogenous estrogen. E2 regulates gene transcription through estrogen receptor α (ERα), but the exact mechanism of KISS1 gene regulation by E2 and ERα remains unclear. We identified key regions for ERα binding and regulation on the mouse Kiss1 promoter by creating 5’ deletions of a Kiss1-reporter plasmid in kisspeptin neuronal cell cultures. Within these regions, we created cis-mutations of putative EREs, revealing one imperfect ERE sequence on the Kiss1 promoter that contributes to ERα regulation in anteroventral periventricular (AVPV) kisspeptin cells. These findings provide further support that E2 bound to ERα acts through an ERE-dependent mechanism for positive feedback in AVPV kisspeptin neurons, providing insight to the molecular mechanism that drives ovulation in females.