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Genetic variants of G‐protein coupled receptors associated with pubertal disorders
BACKGROUND: The human hypothalamic–pituitary‐gonadal (HPG) axis is the regulatory center for pubertal development. This axis involves six G‐protein coupled receptors (GPCRs) encoded by KISS1R, TACR3, PROKR2, GNRHR, LHCGR, and FSHR. METHODS: Previous studies have identified several rare variants of t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134480/ https://www.ncbi.nlm.nih.gov/pubmed/37122876 http://dx.doi.org/10.1002/rmb2.12515 |
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author | Suzuki, Erina Miyado, Mami Kuroki, Yoko Fukami, Maki |
author_facet | Suzuki, Erina Miyado, Mami Kuroki, Yoko Fukami, Maki |
author_sort | Suzuki, Erina |
collection | PubMed |
description | BACKGROUND: The human hypothalamic–pituitary‐gonadal (HPG) axis is the regulatory center for pubertal development. This axis involves six G‐protein coupled receptors (GPCRs) encoded by KISS1R, TACR3, PROKR2, GNRHR, LHCGR, and FSHR. METHODS: Previous studies have identified several rare variants of the six GPCR genes in patients with pubertal disorders. In vitro assays and animal studies have provided information on the function of wild‐type and variant GPCRs. MAIN FINDINGS: Of the six GPCRs, those encoded by KISS1R and TACR3 are likely to reside at the top of the HPG axis. Several loss‐of‐function variants in the six genes were shown to cause late/absent puberty. In particular, variants in KISS1R, TACR3, PROKR2, and GNRHR lead to hypogonadotropic hypogonadism in autosomal dominant, recessive, and oligogenic manners. Furthermore, a few gain‐of‐function variants of KISS1R, PROKR2, and LHCGR have been implicated in precocious puberty. The human HPG axis may contain additional GPCRs. CONCLUSION: The six GPCRs in the HPG axis govern pubertal development through fine‐tuning of hormone secretion. Rare sequence variants in these genes jointly account for a certain percentage of genetic causes of pubertal disorders. Still, much remains to be clarified about the molecular network involving the six GPCRs. |
format | Online Article Text |
id | pubmed-10134480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101344802023-04-28 Genetic variants of G‐protein coupled receptors associated with pubertal disorders Suzuki, Erina Miyado, Mami Kuroki, Yoko Fukami, Maki Reprod Med Biol Mini Reviews BACKGROUND: The human hypothalamic–pituitary‐gonadal (HPG) axis is the regulatory center for pubertal development. This axis involves six G‐protein coupled receptors (GPCRs) encoded by KISS1R, TACR3, PROKR2, GNRHR, LHCGR, and FSHR. METHODS: Previous studies have identified several rare variants of the six GPCR genes in patients with pubertal disorders. In vitro assays and animal studies have provided information on the function of wild‐type and variant GPCRs. MAIN FINDINGS: Of the six GPCRs, those encoded by KISS1R and TACR3 are likely to reside at the top of the HPG axis. Several loss‐of‐function variants in the six genes were shown to cause late/absent puberty. In particular, variants in KISS1R, TACR3, PROKR2, and GNRHR lead to hypogonadotropic hypogonadism in autosomal dominant, recessive, and oligogenic manners. Furthermore, a few gain‐of‐function variants of KISS1R, PROKR2, and LHCGR have been implicated in precocious puberty. The human HPG axis may contain additional GPCRs. CONCLUSION: The six GPCRs in the HPG axis govern pubertal development through fine‐tuning of hormone secretion. Rare sequence variants in these genes jointly account for a certain percentage of genetic causes of pubertal disorders. Still, much remains to be clarified about the molecular network involving the six GPCRs. John Wiley and Sons Inc. 2023-04-27 /pmc/articles/PMC10134480/ /pubmed/37122876 http://dx.doi.org/10.1002/rmb2.12515 Text en © 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Mini Reviews Suzuki, Erina Miyado, Mami Kuroki, Yoko Fukami, Maki Genetic variants of G‐protein coupled receptors associated with pubertal disorders |
title | Genetic variants of G‐protein coupled receptors associated with pubertal disorders |
title_full | Genetic variants of G‐protein coupled receptors associated with pubertal disorders |
title_fullStr | Genetic variants of G‐protein coupled receptors associated with pubertal disorders |
title_full_unstemmed | Genetic variants of G‐protein coupled receptors associated with pubertal disorders |
title_short | Genetic variants of G‐protein coupled receptors associated with pubertal disorders |
title_sort | genetic variants of g‐protein coupled receptors associated with pubertal disorders |
topic | Mini Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134480/ https://www.ncbi.nlm.nih.gov/pubmed/37122876 http://dx.doi.org/10.1002/rmb2.12515 |
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