GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance.

摘要: Abstract Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of hypothalamic-pituitary-gonadal axis, as they regulate basal pulsatile release gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating great importance. One possible factor glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections GLP-1 receptor (GLP-1R) abundant ARC, we hypothesized that GLP-1R signaling could modulate action. Using ovariectomized mice, found GLP-producing fibers come close apposition with neurons; these also contain Glp1r mRNA. Electrophysiological recordings revealed liraglutide (a long-acting agonist) increased potential firing caused a direct membrane depolarization cells brain slices. We determined mRNA decreased after 48-h fast negative state which expression downstream GnRH/luteinizing (LH) potently suppressed. However, activation fasted mice was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions antagonist, exendin(9–39), ad libitum –fed did alter or plasma LH. As whole, data identify novel interaction system but indicate CNS alone critical maintenance during fasting normal feeding.