| Full text | |
| Author(s): |
Canton, Ana Pinheiro Machado
;
Macedo, Delanie Bulcao
;
Abreu, Ana Paula
;
Latronico, Ana Claudia
Total Authors: 4
|
| Document type: | Journal article |
| Source: | JOURNAL OF THE ENDOCRINE SOCIETY; v. 9, n. 2, p. 10-pg., 2025-01-21. |
| Abstract | |
Human puberty is a dynamic biological process determined by the increase in the pulsatile secretion of GnRH triggered by distinct factors not fully understood. Current knowledge reveals fine tuning between an increase in stimulatory factors and a decrease in inhibitory factors, where genetic and epigenetic factors have been indicated as key players in the regulation of puberty onset by distinct lines of evidence. Central precocious puberty (CPP) results from the premature reactivation of pulsatile secretion of GnRH. In the past decade, the identification of genetic causes of CPP has largely expanded, revealing hypothalamic regulatory factors of pubertal timing. Among them, 3 genes associated with CPP are linked to mechanisms involving DNA methylation, reinforcing the strong role of epigenetics underlying this disorder. Loss-of-function mutations in Makorin Ring-Finger Protein 3 (MKRN3) and Delta-Like Non-Canonical Notch Ligand 1 (DLK1), 2 autosomal maternally imprinted genes, have been described as relevant monogenic causes of CPP with the phenotype exclusively associated with paternal transmission. MKRN3 has proven to be a key component of the hypothalamic inhibitory input on GnRH neurons through different mechanisms. Additionally, rare heterozygous variants in the Methyl-CpG-Binding Protein 2 (MECP2), an X-linked gene that is a key factor of DNA methylation machinery, were identified in girls with sporadic CPP with or without neurodevelopmental disorders. In this mini-review, we focus on how the identification of genetic causes of CPP has revealed epigenetic regulators of human pubertal timing, summarizing the latest knowledge on the associations of puberty with MKRN3, DLK1, and MECP2. (AU) | |
| FAPESP's process: | 22/00719-4 - Comprehensive genetic and epigenetic investigation of patients with syndromic central precocious puberty |
| Grantee: | Ana Pinheiro Machado Canton |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/27631-7 - Genetic and epigenetic studies of endocrine disorders related with reproductive axis |
| Grantee: | Ana Claudia Latronico Xavier |
| Support Opportunities: | Research Projects - Thematic Grants |