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dc.contributor.authorGill, John
dc.contributor.authorWang, Oulu
dc.contributor.authorKakar, Shelley
dc.contributor.authorMartinelli, Enzo
dc.contributor.authorCarroll, Rona Stephanie
dc.contributor.authorKaiser, Ursula Brigitte
dc.date.accessioned2012-02-14T03:30:41Z
dc.date.issued2010
dc.identifier.citationGill, John C., Oulu Wang, Shelley Kakar, Enzo Martinelli, Rona S. Carroll, and Ursula B. Kaiser. 2010. Reproductive hormone-dependent and -independent contributions to developmental changes in kisspeptin in GnRH-deficient hypogonadal mice. PLoS ONE 5, no. 7: e11911.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8160883
dc.description.abstractKisspeptin is a potent activator of GnRH-induced gonadotropin secretion and is a proposed central regulator of pubertal onset. In mice, there is a neuroanatomical separation of two discrete kisspeptin neuronal populations, which are sexually dimorphic and are believed to make distinct contributions to reproductive physiology. Within these kisspeptin neuron populations, Kiss1 expression is directly regulated by sex hormones, thereby confounding the roles of sex differences and early activational events that drive the establishment of kisspeptin neurons. In order to better understand sex steroid hormone-dependent and -independent effects on the maturation of kisspeptin neurons, hypogonadal (hpg) mice deficient in GnRH and its downstream effectors were used to determine changes in the developmental kisspeptin expression. In hpg mice, sex differences in Kiss1 mRNA levels and kisspeptin immunoreactivity, typically present at 30 days of age, were absent in the anteroventral periventricular nucleus (AVPV). Although immunoreactive kisspeptin increased from 10 to 30 days of age to levels intermediate between wild type (WT) females and males, corresponding increases in Kiss1 mRNA were not detected. In contrast, the hpg arcuate nucleus (ARC) demonstrated a 10-fold increase in Kiss1 mRNA between 10 and 30 days in both females and males, suggesting that the ARC is a significant center for sex steroid-independent pubertal kisspeptin expression. Interestingly, the normal positive feedback response of AVPV kisspeptin neurons to estrogen observed in WT mice was lost in hpg females, suggesting that exposure to reproductive hormones during development may contribute to the establishment of the ovulatory gonadotropin surge mechanism. Overall, these studies suggest that the onset of pubertal kisspeptin expression is not dependent on reproductive hormones, but that gonadal sex steroids critically shape the hypothalamic kisspeptin neuronal subpopulations to make distinct contributions to the activation and control of the reproductive hormone cascade at the time of puberty.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.pone.0011911en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912854/pdf/en_US
dash.licenseLAA
dc.subjectcell biologyen_US
dc.subjectneuronal signaling mechanismsen_US
dc.subjectneuroscienceen_US
dc.subjectneural homeostasisen_US
dc.subjectneurodevelopmenten_US
dc.subjectdiabetes and endocrinologyen_US
dc.subjectneuroendocrinology and pituitaryen_US
dc.subjectreproductive endocrinologyen_US
dc.titleReproductive Hormone-Dependent and -Independent Contributions to Developmental Changes in Kisspeptin in GnRH-Deficient Hypogonadal Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorGill, John
dc.date.available2012-02-14T03:30:41Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Surgery-Children's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0011911*
dash.contributor.affiliatedGill, John
dash.contributor.affiliatedCarroll, Rona
dash.contributor.affiliatedKaiser, Ursula


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