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FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice
Disclosure: L. Maione: Consulting Fee; Self; Pfizer, Inc., Ipsen. L. Naule: None. C. Li: None. M. Magnuson: None. J. Young: Consulting Fee; Self; Serono Laboratories, Ferring Pharmaceuticals. R.S. Carroll: None. U.B. Kaiser: None. Introduction: The hypothalamic-pituitary-gonadal (HPG) axis is regula...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10555760/ http://dx.doi.org/10.1210/jendso/bvad114.1216 |
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author | Maione, Luigi Naule, Lydie Li, Chloe Magnuson, Melissa Young, Jacques Carroll, Rona Stephanie Kaiser, Ursula B |
author_facet | Maione, Luigi Naule, Lydie Li, Chloe Magnuson, Melissa Young, Jacques Carroll, Rona Stephanie Kaiser, Ursula B |
author_sort | Maione, Luigi |
collection | PubMed |
description | Disclosure: L. Maione: Consulting Fee; Self; Pfizer, Inc., Ipsen. L. Naule: None. C. Li: None. M. Magnuson: None. J. Young: Consulting Fee; Self; Serono Laboratories, Ferring Pharmaceuticals. R.S. Carroll: None. U.B. Kaiser: None. Introduction: The hypothalamic-pituitary-gonadal (HPG) axis is regulated by pulsatile GnRH secretion and its action on the anterior pituitary, leading to the synthesis and secretion of LH and FSH. KNDy neurons, expressing kisspeptin, neurokinin B and dynorphin A, are the GnRH/LH pulse generator and are key regulators of puberty and fertility. The HPG axis is active during prenatal and early postnatal life in humans and rodents, but then remains quiescent until puberty in both species. The response of gonadotropes to exogenous upstream GnRH signals such as kisspeptin and neurokinin during prepubertal development in mice is unknown. Aim: To conduct a systematic assessment of LH responsiveness to exogenous kisspeptin and to the neurokinin-3 receptor agonist senktide at regular intervals postnatally and across pubertal maturation in mice. Materials and Methods: Male and female J129Sv mice were treated with intraperitoneal injections of kisspeptin-10 (0.0023 nmol/g), senktide (0.023 nmol/g) or vehicle every 3 days from postnatal day (PND) 10 until completion of puberty. Serum LH was measured by an ultra-sensitive ELISA at baseline and 15 minutes after injection. Results: Prepubertal mice responded in an age-dependent and sexually dimorphic manner to kisspeptin and senktide. LH levels increased following kisspeptin stimulation in both sexes, but responses were higher in females than in males from PND10 to PND16. The highest response was observed at PND10, with a pattern of decreasing response with advancing age. Senktide induced a robust increase in serum LH in females from PND10 to PND16, with a decrease in response with age, similar to that observed after kisspeptin treatment. In contrast, in males there was no increase in serum LH in response to senktide at any age. No difference in the onset of puberty or body weight was observed across treatment groups. Conclusions: The assessment of serum LH levels following IP administration of kisspeptin and senktide in prepubertal male and female mice demonstrated distinct age and sexually-dimorphic patterns of LH responses to GnRH upstream signals. LH responses are maximal at early ages with a decreasing pattern overtime, and are higher in females than in males, suggesting a different distribution of kisspeptin/neurokinin receptors or the presence of different and/or additional restraining factors on GnRH/LH in the two sexes. These findings provide new evidence for sexual dimorphism of the HPG axis in mice early in postnatal life, prior to the onset of puberty. Presentation: Friday, June 16, 2023 |
format | Online Article Text |
id | pubmed-10555760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105557602023-10-07 FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice Maione, Luigi Naule, Lydie Li, Chloe Magnuson, Melissa Young, Jacques Carroll, Rona Stephanie Kaiser, Ursula B J Endocr Soc Neuroendocrinology & Pituitary Disclosure: L. Maione: Consulting Fee; Self; Pfizer, Inc., Ipsen. L. Naule: None. C. Li: None. M. Magnuson: None. J. Young: Consulting Fee; Self; Serono Laboratories, Ferring Pharmaceuticals. R.S. Carroll: None. U.B. Kaiser: None. Introduction: The hypothalamic-pituitary-gonadal (HPG) axis is regulated by pulsatile GnRH secretion and its action on the anterior pituitary, leading to the synthesis and secretion of LH and FSH. KNDy neurons, expressing kisspeptin, neurokinin B and dynorphin A, are the GnRH/LH pulse generator and are key regulators of puberty and fertility. The HPG axis is active during prenatal and early postnatal life in humans and rodents, but then remains quiescent until puberty in both species. The response of gonadotropes to exogenous upstream GnRH signals such as kisspeptin and neurokinin during prepubertal development in mice is unknown. Aim: To conduct a systematic assessment of LH responsiveness to exogenous kisspeptin and to the neurokinin-3 receptor agonist senktide at regular intervals postnatally and across pubertal maturation in mice. Materials and Methods: Male and female J129Sv mice were treated with intraperitoneal injections of kisspeptin-10 (0.0023 nmol/g), senktide (0.023 nmol/g) or vehicle every 3 days from postnatal day (PND) 10 until completion of puberty. Serum LH was measured by an ultra-sensitive ELISA at baseline and 15 minutes after injection. Results: Prepubertal mice responded in an age-dependent and sexually dimorphic manner to kisspeptin and senktide. LH levels increased following kisspeptin stimulation in both sexes, but responses were higher in females than in males from PND10 to PND16. The highest response was observed at PND10, with a pattern of decreasing response with advancing age. Senktide induced a robust increase in serum LH in females from PND10 to PND16, with a decrease in response with age, similar to that observed after kisspeptin treatment. In contrast, in males there was no increase in serum LH in response to senktide at any age. No difference in the onset of puberty or body weight was observed across treatment groups. Conclusions: The assessment of serum LH levels following IP administration of kisspeptin and senktide in prepubertal male and female mice demonstrated distinct age and sexually-dimorphic patterns of LH responses to GnRH upstream signals. LH responses are maximal at early ages with a decreasing pattern overtime, and are higher in females than in males, suggesting a different distribution of kisspeptin/neurokinin receptors or the presence of different and/or additional restraining factors on GnRH/LH in the two sexes. These findings provide new evidence for sexual dimorphism of the HPG axis in mice early in postnatal life, prior to the onset of puberty. Presentation: Friday, June 16, 2023 Oxford University Press 2023-10-05 /pmc/articles/PMC10555760/ http://dx.doi.org/10.1210/jendso/bvad114.1216 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Neuroendocrinology & Pituitary Maione, Luigi Naule, Lydie Li, Chloe Magnuson, Melissa Young, Jacques Carroll, Rona Stephanie Kaiser, Ursula B FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice |
title | FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice |
title_full | FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice |
title_fullStr | FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice |
title_full_unstemmed | FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice |
title_short | FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice |
title_sort | fri281 sexual dimorphism in the lh responses to kisspeptin and senktide administration in prepubertal mice |
topic | Neuroendocrinology & Pituitary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10555760/ http://dx.doi.org/10.1210/jendso/bvad114.1216 |
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