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Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women

CONTEXT: Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE: To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion. DESIGN: Women were treated with neurokinin-3 receptor...

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Autores principales: Skorupskaite, Karolina, George, Jyothis T., Veldhuis, Johannes D., Millar, Robert P., Anderson, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155690/
https://www.ncbi.nlm.nih.gov/pubmed/27636018
http://dx.doi.org/10.1210/jc.2016-2132
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author Skorupskaite, Karolina
George, Jyothis T.
Veldhuis, Johannes D.
Millar, Robert P.
Anderson, Richard A.
author_facet Skorupskaite, Karolina
George, Jyothis T.
Veldhuis, Johannes D.
Millar, Robert P.
Anderson, Richard A.
author_sort Skorupskaite, Karolina
collection PubMed
description CONTEXT: Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE: To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion. DESIGN: Women were treated with neurokinin-3 receptor (NK3R) antagonist followed by transdermal estradiol to induce LH secretion 48 hours later, with kisspeptin-10 or vehicle infusion during estrogen administration in a 2-way crossover study. SETTING: Clinical research facility. PATIENTS OR OTHER PARTICIPANTS: Healthy females with regular menses. INTERVENTION(S): NK3R antagonist AZD4901 40 mg twice daily orally was taken from cycle day 4–6 for 6 days (n = 10, with 10 no treatment controls). Transdermal estradiol patches (200 μg/d) were applied after 5 days of NK3R antagonist treatment. At 24-hour estradiol treatment, women were randomized to 7-hour kisspeptin-10 (4 μg/kg/h) or vehicle iv infusion, with the alternate infusion in a subsequent cycle. MAIN OUTCOME MEASURE(S): Plasma gonadotropin and estradiol secretion. RESULTS: After an initial suppression, LH secretion was increased 48 hours after estradiol treatment. Kisspeptin-10 increased LH secretion during the inhibitory phase, and LH remained elevated beyond the discontinuation of kisspeptin-10 infusion. NK3R antagonist decreased LH pulse frequency (0.5 ± 0.2 vs 0.7 ± 0.2 pulses/h, P < .05) and stimulated FSH response to kisspeptin-10 infusion (10.7 ± 11.0 vs 5.0 ± 3.6 IU/L, P < .05) with a nonsignificant rise in LH. The duration of LH response was blunted, with LH being lower at 48 hours (7.5 ± 4.8 vs 15.0 ± 11.4 IU/L, P < .05). CONCLUSIONS: These data demonstrate that NKB signaling regulates GnRH/LH secretion in normal women, and is predominantly proximal to kisspeptin in mediating estrogenic positive and negative feedback on LH secretion.
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spelling pubmed-51556902016-12-28 Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women Skorupskaite, Karolina George, Jyothis T. Veldhuis, Johannes D. Millar, Robert P. Anderson, Richard A. J Clin Endocrinol Metab Original Articles CONTEXT: Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE: To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion. DESIGN: Women were treated with neurokinin-3 receptor (NK3R) antagonist followed by transdermal estradiol to induce LH secretion 48 hours later, with kisspeptin-10 or vehicle infusion during estrogen administration in a 2-way crossover study. SETTING: Clinical research facility. PATIENTS OR OTHER PARTICIPANTS: Healthy females with regular menses. INTERVENTION(S): NK3R antagonist AZD4901 40 mg twice daily orally was taken from cycle day 4–6 for 6 days (n = 10, with 10 no treatment controls). Transdermal estradiol patches (200 μg/d) were applied after 5 days of NK3R antagonist treatment. At 24-hour estradiol treatment, women were randomized to 7-hour kisspeptin-10 (4 μg/kg/h) or vehicle iv infusion, with the alternate infusion in a subsequent cycle. MAIN OUTCOME MEASURE(S): Plasma gonadotropin and estradiol secretion. RESULTS: After an initial suppression, LH secretion was increased 48 hours after estradiol treatment. Kisspeptin-10 increased LH secretion during the inhibitory phase, and LH remained elevated beyond the discontinuation of kisspeptin-10 infusion. NK3R antagonist decreased LH pulse frequency (0.5 ± 0.2 vs 0.7 ± 0.2 pulses/h, P < .05) and stimulated FSH response to kisspeptin-10 infusion (10.7 ± 11.0 vs 5.0 ± 3.6 IU/L, P < .05) with a nonsignificant rise in LH. The duration of LH response was blunted, with LH being lower at 48 hours (7.5 ± 4.8 vs 15.0 ± 11.4 IU/L, P < .05). CONCLUSIONS: These data demonstrate that NKB signaling regulates GnRH/LH secretion in normal women, and is predominantly proximal to kisspeptin in mediating estrogenic positive and negative feedback on LH secretion. Endocrine Society 2016-12 2016-09-16 /pmc/articles/PMC5155690/ /pubmed/27636018 http://dx.doi.org/10.1210/jc.2016-2132 Text en https://creativecommons.org/licenses/by/4.0/ This article has been published under the terms of the Creative Commons Attribution License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
spellingShingle Original Articles
Skorupskaite, Karolina
George, Jyothis T.
Veldhuis, Johannes D.
Millar, Robert P.
Anderson, Richard A.
Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
title Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
title_full Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
title_fullStr Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
title_full_unstemmed Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
title_short Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
title_sort interactions between neurokinin b and kisspeptin in mediating estrogen feedback in healthy women
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155690/
https://www.ncbi.nlm.nih.gov/pubmed/27636018
http://dx.doi.org/10.1210/jc.2016-2132
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