Regulation ofKiss1andDynorphinGene Expression in the Murine Brain by Classical and Nonclassical Estrogen Receptor Pathways

Open Access
Publisher Website
Google Scholar
Abstract
Kisspeptin is a product of theKiss1gene and is expressed in the forebrain. Neurons that expressKiss1play a crucial role in the regulation of pituitary luteinizing hormone secretion and reproduction. These neurons are the direct targets for the action of estradiol-17β (E2), which acts via the estrogen receptor α isoform (ERα) to regulateKiss1expression. In the arcuate nucleus (Arc), where thedynorphingene (Dyn) is expressed inKiss1neurons, E2inhibits the expression ofKiss1mRNA. However, E2induces the expression ofKiss1in the anteroventral periventricular nucleus (AVPV). The mechanism for differential regulation ofKiss1in the Arc and AVPV by E2is unknown. ERα signals through multiple pathways, which can be categorized as either classical, involving the estrogen response element (ERE), or nonclassical, involving ERE-independent mechanisms. To elucidate the molecular basis for the action of E2onKiss1andDynexpression, we studied the effects of E2onKiss1andDynmRNAs in the brains of mice bearing targeted alterations in the ERα signaling pathways. We found that stimulation ofKiss1expression by E2in the AVPV and inhibition ofDynin the Arc required an ERE-dependent pathway, whereas the inhibition ofKiss1expression by E2in the Arc involved ERE-independent mechanisms. Thus, distinct ERα signaling pathways can differentially regulate the expression of identical genes across different brain regions, and E2can act within the same neuron through divergent ERα signaling pathways to regulate different neurotransmitter genes.