Affiliation:
1. Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan
2. Department of Food and Nutrition Beppu University Oita Japan
3. Department of Genome Medicine, National Center for Child Health and Development Tokyo Japan
4. Division of Collaborative Research, National Center for Child Health and Development Tokyo Japan
5. Division of Diversity Research National Research Institute for Child Health and Development Tokyo Japan
Abstract
AbstractBackgroundThe 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.MethodsPrevious 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 FindingsOf 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.ConclusionThe 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.
Funder
Japan Agency for Medical Research and Development
Japan Society for the Promotion of Science
National Center for Child Health and Development
Takeda Science Foundation
Subject
Cell Biology,Reproductive Medicine
Cited by
4 articles.
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