Evidence that neurokinin B controls basal gonadotropin-releasing hormone secretion but is not critical for estrogen-positive feedback in sheep

dc.contributor.authorLi, Qun
dc.contributor.authorMillar, Robert P.
dc.contributor.authorClarke, Iain J.
dc.contributor.authorSmith, Jeremy T.
dc.date.accessioned2015-10-05T07:40:00Z
dc.date.available2015-10-05T07:40:00Z
dc.date.issued2015-05
dc.description.abstractBACKGROUND : Loss-of-function mutations in genes encoding kisspeptin or neurokinin B (NKB) or their receptors cause infertility. NKB is coproduced in kisspeptin neurons in the arcuate nucleus (ARC), and these neurons also produce the NKB receptor (NK3R), allowing autosynaptic function. We tested the hypothesis that NKB action in ARC kisspeptin neurons is aligned with increased pulsatile secretion of luteinizing hormone (LH) and/or activation of the estrogen-induced LH surge in ewes. METHODS : Using in situ hybridization and immunohistochemistry, we examined NKB expression in kisspeptin neurons during the ovine estrous cycle. We infused kisspeptin, senktide (an NK3R agonist), or dynorphin into the lateral ventricle during the luteal phase of the estrous cycle to determine effects on pulsatile LH secretion. Finally, we examined the effect of an NK3R antagonist (MRK-08) in ovariectomized ewes. RESULTS : NKB (Tac3) mRNA expression in mid-ARC kisspeptin neurons was elevated during the mid-to-late follicular phase of the estrous cycle. The number of NKB-immunoreactive cells and NKB/kisspeptin terminals in the median eminence was similar during the estrous cycle. Kisspeptin and senktide increased LH pulse frequency and mean LH levels. Central MRK-08 infusion eliminated the LH pulses but did not prevent an estrogen-positive feedback on LH secretion. CONCLUSIONS : NKB expression in ARC kisspeptin neurons is upregulated during the late follicular phase of the estrous cycle, when the pulsatile secretion of gonadotropin-releasing hormone (GnRH)/LH is maximal. When GnRH/LH secretion is minimal, central senktide infusion induces LH secretion, similar to the response to kisspeptin. Although the increase in LH in response to senktide appeared surge-like, we did not observe any change in the surge following NK3R antagonist treatment. We conclude that NKB plays a role in increasing basal GnRH/LH pulsatility in the follicular phase of the cycle but is not essential for estrogen-induced positive feedback.en_ZA
dc.description.librarianhb2015en_ZA
dc.description.sponsorshipAustralian Research Council Discovery Project DP120100521.en_ZA
dc.description.urihttp://www.karger.com/Journal/Home/223855en_ZA
dc.identifier.citationLi, Q, Millar, RP, Clarke, IJ & Smith, JT 2015, 'Evidence that neurokinin B controls basal gonadotropin-releasing hormone secretion but is not critical for estrogen-positive feedback in sheep', Neuroendocrinology, vol. 101, no. 2, pp. 161-174.en_ZA
dc.identifier.issn0028-3835 (print)
dc.identifier.issn1423-0194 (online)
dc.identifier.other10.1159/000377702
dc.identifier.urihttp://hdl.handle.net/2263/50155
dc.language.isoenen_ZA
dc.publisherKargeren_ZA
dc.rights© 2015 S. Karger AG, Basel.en_ZA
dc.subjectKiss1en_ZA
dc.subjectDynorphinen_ZA
dc.subjectEstrous cycleen_ZA
dc.subjectOvulationen_ZA
dc.subjectNeurokinin B (NKB)en_ZA
dc.subjectKisspeptin neuronsen_ZA
dc.titleEvidence that neurokinin B controls basal gonadotropin-releasing hormone secretion but is not critical for estrogen-positive feedback in sheepen_ZA
dc.typePostprint Articleen_ZA

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