title: The physiological role of arcuate kisspeptin neurons in the control of reproductive function in female rats.
abstract: Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity.
authors.affiliation: Section of Investigative Medicine (K.E.B., J.S.K.-J., J.V.G., E.K.H., E.L.T., M.L.S., A.H.S., H.C.G., A.K.M., W.S.D., S.R.B., K.G.M.) and Institute of Reproductive and Developmental Biology (J.M.M., S.F.), Imperial College London, London W12 0NN, United Kingdom; and Division of Women's Health (M.H.H., X.F.L., K.T.O.), School of Medicine, King's College London, London SE1 1UL, United Kingdom.
authors.forename: K E
authors.initials: KE
authors.lastname: Beale
authors.forename: J S
authors.initials: JS
authors.lastname: Kinsey-Jones
authors.forename: J V
authors.initials: JV
authors.lastname: Gardiner
authors.forename: E K
authors.initials: EK
authors.lastname: Harrison
authors.forename: E L
authors.initials: EL
authors.lastname: Thompson
authors.forename: M H
authors.initials: MH
authors.lastname: Hu
authors.forename: M L
authors.initials: ML
authors.lastname: Sleeth
authors.forename: A H
authors.initials: AH
authors.lastname: Sam
authors.forename: H C
authors.initials: HC
authors.lastname: Greenwood
authors.forename: A K
authors.initials: AK
authors.lastname: McGavigan
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
authors.forename: J M
authors.initials: JM
authors.lastname: Mora
authors.forename: X F
authors.initials: XF
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Franks
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.forename: K T
authors.initials: KT
authors.lastname: O'Byrne
authors.forename: K G
authors.initials: KG
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D004958:Estradiol / Q000378:metabolism; D030762:Estrous Cycle; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007118:Immunoassay; D059648:Kisspeptins / Q000235:genetics / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics; D012098:Reproduction / Q000502:physiology*; D013997:Time Factors
chemical_list: C491406:Kiss1 protein, rat; D059648:Kisspeptins; D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D004958:Estradiol; D007986:Luteinizing Hormone