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Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women

CONTEXT: Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown. OBJECTIVE: To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian fol...

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Autores principales: Skorupskaite, Karolina, George, Jyothis T., Veldhuis, Johannes D., Anderson, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761486/
https://www.ncbi.nlm.nih.gov/pubmed/29040622
http://dx.doi.org/10.1210/jc.2017-01306
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author Skorupskaite, Karolina
George, Jyothis T.
Veldhuis, Johannes D.
Anderson, Richard A.
author_facet Skorupskaite, Karolina
George, Jyothis T.
Veldhuis, Johannes D.
Anderson, Richard A.
author_sort Skorupskaite, Karolina
collection PubMed
description CONTEXT: Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown. OBJECTIVE: To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in healthy women. DESIGN: Open investigation of the effects of a neurokinin-3 receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle. SETTING: Clinical research facility. PATIENTS OR OTHER PARTICIPANTS: Healthy women with regular menses (n = 13). INTERVENTION(S): NK3Ra MLE4901 40 mg taken orally twice daily from cycle day 5 to 6 for 7 days. MAIN OUTCOME MEASURE(S): LH secretion, ovarian follicle growth, and timing of ovulation. RESULTS: NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment [mean cycle day ± standard error of the mean (SEM), 22 ± 1 days vs 15 ± 1 days in control cycles; P = 0.0006]. Follicle growth (mean diameter at the end of administration of NK3Ra administration ± SEM, 9.3 ± 0.4 mm vs 15.1 ± 0.9 mm in control cycles; P < 0.0001) and rising estradiol concentrations (mean ± SEM, 166 ± 29 pmol/L vs 446 ± 86 pmol/L in control cycles; P < 0.0001) were prevented. After treatment, follicle development resumed and normal preovulatory follicle diameter and estradiol concentrations were demonstrated. Postovulatory progesterone rise was similarly delayed (peak cycle day, 30 ± 2 vs 22 ± 1; P = 0.002) and cycle length was prolonged (35 ± 1 days vs 29 ± 1 days in control cycles; P = 0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 mean urinary progesterone levels ± SEM, 58 ± 10 pmol/mol vs 48±7 pmol/mol creatinine in control cycles; nonsignificant). CONCLUSION: These data demonstrate the involvement of NKB-NK3R signaling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women.
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spelling pubmed-57614862018-01-23 Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women Skorupskaite, Karolina George, Jyothis T. Veldhuis, Johannes D. Anderson, Richard A. J Clin Endocrinol Metab Clinical Research Articles CONTEXT: Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown. OBJECTIVE: To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in healthy women. DESIGN: Open investigation of the effects of a neurokinin-3 receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle. SETTING: Clinical research facility. PATIENTS OR OTHER PARTICIPANTS: Healthy women with regular menses (n = 13). INTERVENTION(S): NK3Ra MLE4901 40 mg taken orally twice daily from cycle day 5 to 6 for 7 days. MAIN OUTCOME MEASURE(S): LH secretion, ovarian follicle growth, and timing of ovulation. RESULTS: NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment [mean cycle day ± standard error of the mean (SEM), 22 ± 1 days vs 15 ± 1 days in control cycles; P = 0.0006]. Follicle growth (mean diameter at the end of administration of NK3Ra administration ± SEM, 9.3 ± 0.4 mm vs 15.1 ± 0.9 mm in control cycles; P < 0.0001) and rising estradiol concentrations (mean ± SEM, 166 ± 29 pmol/L vs 446 ± 86 pmol/L in control cycles; P < 0.0001) were prevented. After treatment, follicle development resumed and normal preovulatory follicle diameter and estradiol concentrations were demonstrated. Postovulatory progesterone rise was similarly delayed (peak cycle day, 30 ± 2 vs 22 ± 1; P = 0.002) and cycle length was prolonged (35 ± 1 days vs 29 ± 1 days in control cycles; P = 0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 mean urinary progesterone levels ± SEM, 58 ± 10 pmol/mol vs 48±7 pmol/mol creatinine in control cycles; nonsignificant). CONCLUSION: These data demonstrate the involvement of NKB-NK3R signaling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women. Endocrine Society 2017-10-12 /pmc/articles/PMC5761486/ /pubmed/29040622 http://dx.doi.org/10.1210/jc.2017-01306 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 Clinical Research Articles
Skorupskaite, Karolina
George, Jyothis T.
Veldhuis, Johannes D.
Anderson, Richard A.
Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
title Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
title_full Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
title_fullStr Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
title_full_unstemmed Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
title_short Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
title_sort neurokinin b regulates gonadotropin secretion, ovarian follicle growth, and the timing of ovulation in healthy women
topic Clinical Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761486/
https://www.ncbi.nlm.nih.gov/pubmed/29040622
http://dx.doi.org/10.1210/jc.2017-01306
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