Neurokinin B signaling in the female rat : a novel link between stress and reproduction

dc.contributor.authorGrachev, Pasha
dc.contributor.authorLi, X.F.
dc.contributor.authorHu, M.H.
dc.contributor.authorLi, S.Y.
dc.contributor.authorMillar, Robert P.
dc.contributor.authorLightman, Stafford L.
dc.contributor.authorO'Byrne, Kevin T.
dc.date.accessioned2014-12-10T06:04:53Z
dc.date.available2014-12-10T06:04:53Z
dc.date.issued2014-04-07
dc.description.abstractAcute systemic stress disrupts reproductive function by inhibiting pulsatile gonadotropin secretion. The underlying mechanism involves stress-induced suppression of the GnRH pulse generator, the functional unit of which is considered to be the hypothalamic arcuate nucleus kisspeptin/neurokinin B/dynorphinAneurons. Agonists of the neurokininB(NKB) receptor (NK3R) have beenshown to suppress the GnRH pulse generator, in a dynorphin A (Dyn)-dependent fashion, under hypoestrogenic conditions, and Dyn has been well documented to mediate several stress-related central regulatory functions. We hypothesized that the NKB/Dyn signaling cascade is required for stressinduced suppression of the GnRH pulse generator. To investigate this ovariectomized rats, iv administered with Escherichia coli lipopolysaccharide (LPS) following intracerebroventricular pretreatment with NK3R or -opioid receptor (Dyn receptor) antagonists, were subjected to frequent blood sampling for hormone analysis. Antagonism of NK3R, but not -opioid receptor, blocked the suppressive effect of LPS challengeonLHpulse frequency. Neither antagonist affected LPS-induced corticosterone secretion. Hypothalamic arcuate nucleus NKB neurons project to the paraventricular nucleus, the major hypothalamic source of the stress-related neuropeptides CRH and arginine vasopressin (AVP), which have been implicated in the stress-induced suppression of the hypothalamic- pituitary-gonadal axis. A separate group of ovariectomized rats was, therefore, used to address the potential involvement of central CRH and/or AVP signaling in the suppression of LH pulsatility induced by intracerebroventricular administration of a selective NK3R agonist, senktide. Neither AVP nor CRH receptor antagonists affected the senktide-induced suppression of the LH pulse; however, antagonism of type 2 CRH receptors attenuated the accompanying elevation of corticosterone levels. These data indicate that the suppression of the GnRH pulse generator by acute systemic stress requires hypothalamic NKB/NK3R signaling and that any involvement of CRH therewith is functionally upstream of NKB.en_ZA
dc.description.embargo2015-07-30en_ZA
dc.description.librarianam2014en_ZA
dc.description.urihttp://press.endocrine.org/journal/endoen_ZA
dc.identifier.citationGrachev, P, Li, XF, Hu, MH, Li, SY, Millar, RP, Lightman, SL & O'Byrne, KT 2014, 'Neurokinin B signaling in the female rat : a novel link between stress and reproduction', Endocrinology, vol. 155, no. 7, pp. 2589-2601.en_ZA
dc.identifier.issn0013-7227 (print)
dc.identifier.issn1945-7170 (online)
dc.identifier.other10.1210/en.2013-2038
dc.identifier.urihttp://hdl.handle.net/2263/42897
dc.language.isoenen_ZA
dc.publisherThe Endocrine Societyen_ZA
dc.rights© 2014 The Endocrine Societyen_ZA
dc.subjectStressen_ZA
dc.subjectReproductionen_ZA
dc.subjectAcute systemic stressen_ZA
dc.subjectGnRH pulse generatoren_ZA
dc.subjectNeurokinin B (NKB)en_ZA
dc.subjectNKB/NK3R signalingen_ZA
dc.titleNeurokinin B signaling in the female rat : a novel link between stress and reproductionen_ZA
dc.typeArticleen_ZA

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