Precocious Puberty in Boys with <em>NR0B1</em> Variants

Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic <i>NR0B1</i> variants, which typically cause X-linked adrenal hypoplasia congeni...

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Main Authors: Atsushi Hattori, Maki Fukami
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Endocrines
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Online Access:https://www.mdpi.com/2673-396X/5/4/38
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author Atsushi Hattori
Maki Fukami
author_facet Atsushi Hattori
Maki Fukami
author_sort Atsushi Hattori
collection DOAJ
description Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic <i>NR0B1</i> variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with <i>NR0B1</i> variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, <i>NR0B1</i> variants cause PP. PP associated with <i>NR0B1</i> variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and <i>NR0B1</i> variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with <i>NR0B1</i> variants.
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spelling doaj-art-b2400be3bdf544ff9a313be76c8e2f572024-12-27T14:23:05ZengMDPI AGEndocrines2673-396X2024-11-015452953710.3390/endocrines5040038Precocious Puberty in Boys with <em>NR0B1</em> VariantsAtsushi Hattori0Maki Fukami1Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanPrecocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic <i>NR0B1</i> variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with <i>NR0B1</i> variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, <i>NR0B1</i> variants cause PP. PP associated with <i>NR0B1</i> variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and <i>NR0B1</i> variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with <i>NR0B1</i> variants.https://www.mdpi.com/2673-396X/5/4/38DAX1<i>NR0B1</i>precocious pubertyLeydig cell
spellingShingle Atsushi Hattori
Maki Fukami
Precocious Puberty in Boys with <em>NR0B1</em> Variants
Endocrines
DAX1
<i>NR0B1</i>
precocious puberty
Leydig cell
title Precocious Puberty in Boys with <em>NR0B1</em> Variants
title_full Precocious Puberty in Boys with <em>NR0B1</em> Variants
title_fullStr Precocious Puberty in Boys with <em>NR0B1</em> Variants
title_full_unstemmed Precocious Puberty in Boys with <em>NR0B1</em> Variants
title_short Precocious Puberty in Boys with <em>NR0B1</em> Variants
title_sort precocious puberty in boys with em nr0b1 em variants
topic DAX1
<i>NR0B1</i>
precocious puberty
Leydig cell
url https://www.mdpi.com/2673-396X/5/4/38
work_keys_str_mv AT atsushihattori precociouspubertyinboyswithemnr0b1emvariants
AT makifukami precociouspubertyinboyswithemnr0b1emvariants