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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2017
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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. |
format | Online Article Text |
id | pubmed-5761486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
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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