气候变化领域集成服务门户(CCPortal): Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment

CCPortal

DOI	10.1073/pnas.2012339118
	Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment
	Constantin S.; Reynolds D.; Oh A.; Pizano K.; Wray S.
发表日期	2021
ISSN	00278424
卷号	118 期号:1
英文摘要	Fertility relies upon pulsatile release of gonadotropin-releasing hormone (GnRH) that drives pulsatile luteinizing hormone secretion. Kisspeptin (KP) neurons in the arcuate nucleus are at the center of the GnRH pulse generation and the steroid feedback control of GnRH secretion. However, KP evokes a long-lasting response in GnRH neurons that is hard to reconcile with periodic GnRH activity required to drive GnRH pulses. Using calcium imaging, we show that 1) the tetrodotoxin-insensitive calcium response evoked by KP relies upon the ongoing activity of canonical transient receptor potential channels maintaining voltage-gated calcium channels in an activated state, 2) the duration of the calcium response is determined by the rate of resynthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), and 3) nitric oxide terminates the calcium response by facilitating the resynthesis of PIP2 via the canonical pathway guanylyl cyclase/3′,5′-cyclic guanosine monophosphate/protein kinase G. In addition, our data indicate that exposure to nitric oxide after KP facilitates the calcium response to a subsequent KP application. This effect was replicated using electrophysiology on GnRH neurons in acute brain slices. The interplay between KP and nitric oxide signaling provides a mechanism for modulation of the refractory period of GnRH neurons after KP exposure and places nitric oxide as an important component for tonic GnRH neuronal pulses. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Fertility; GnRH; Kisspeptin; Nitric oxide; Pulse
语种	英语
scopus关键词	calcium; cyclic GMP; cyclic GMP dependent protein kinase; gonadorelin; guanylate cyclase; kisspeptin; nitric oxide; phosphatidylinositol 4,5 bisphosphate; adult; animal experiment; Article; brain slice; chemical interaction; controlled study; embryo; male; mouse; nervous system electrophysiology; neuromodulation; nonhuman; priority journal; signal transduction; synthesis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181158
作者单位	Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, United States
推荐引用方式 GB/T 7714	Constantin S.,Reynolds D.,Oh A.,et al. Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment[J],2021,118(1).
APA	Constantin S.,Reynolds D.,Oh A.,Pizano K.,&Wray S..(2021).Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment.Proceedings of the National Academy of Sciences of the United States of America,118(1).
MLA	Constantin S.,et al."Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021).