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León, S, Fergani, C, Talbi, R, Maguire, CA, Gerutshang, A, Seminara, SB and Navarro, VM (2020) Tachykinin signaling is required for the induction of the preovulatory LH surge and normal LH pulses. Neuroendocrinology. ISSN 1423-0194
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Abstract
Tachykinins (NKA, NKB and Substance P) are important components of the neuroendocrine control of reproduction by directly stimulating Kiss1 neurons to control GnRH pulsatility, essential for reproduction. Despite this role of tachykinins for successful reproduction, knockout mice for Tac1 (NKA/SP) and Tac2 (NKB) genes are fertile, resembling the phenotype of human patients bearing NKB signaling mutations, who often reverse their hypogonadal phenotype. This suggests the existence of compensatory mechanisms among the different tachykinin ligand-receptor systems, to maintain reproduction in the absence of one of them. In order to test this hypothesis, we generated complete tachykinin deficient mice (Tac1/Tac2KO). Male mice displayed delayed puberty onset and decreased LH pulsatility (frequency and amplitude of LH pulses) but preserved fertility. However, females did not show signs of puberty onset (first estrus) within 45 days after vaginal opening, displayed low frequency (but normal amplitude) of LH pulses and 80% of them remained infertile. Further evaluation identified a complete absence of the preovulatory LH surge in Tac1/Tac2KO females as well as in WT females treated with NKB or SP receptor antagonists. These data confirmed a fundamental role for tachykinins in the timing of puberty onset and LH pulsatility and uncovered a role of tachykinin signaling in the facilitation of the preovulatory LH surge. Overall, these findings indicate that tachykinin signaling plays a dominant role in the control of ovulation, with potential implications as pathogenic mechanism and therapeutic target to improve reproductive outcomes in women with ovulation impairments.
| Item Type: | Article |
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| Additional Information: | This is the accepted manuscript version of an article published by S. Karger AG in Neuroendocrinology 2020 available on www.karger.com/Article/FullText/10.1159/000509222 |
| Uncontrolled Keywords: | 1103 Clinical Sciences, 1109 Neurosciences |
| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QL Zoology |
| Divisions: | Biological & Environmental Sciences (from Sep 19) |
| Publisher: | Karger Publishers |
| Related URLs: | |
| Date Deposited: | 18 Jun 2020 10:32 |
| Last Modified: | 04 Sep 2021 07:09 |
| DOI or ID number: | 10.1159/000509222 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/13122 |
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