DLK1 Is a Novel Link Between Reproduction and Metabolism

Gomes, Larissa; Cunha-Silva, Marina; Crespo, Raiane P; Ramos, Carolina; Montenegro, Luciana Ribeiro; Canton, Ana Pinheiro Machado; Lees, Melissa; Spoudeas, Helen; Dauber, Andrew; Macedo, Delanie B.; Bessa, Danielle; Maciel, Gustavo Arantes Rosa; Baracat, Edmund C.; Jorge, Alexander A L; Mendonca, Berenice B.; Brito, Vinícius Nahime; Latrônico, Ana Claudia

doi:10.1210/jc.2018-02010

Cited by 81 publications

(70 citation statements)

References 30 publications

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“…The more prevalent features at adulthood were central obesity, early onset glucose intolerance/type 2 diabetes, and hyperlipidemia. These metabolic alterations were similar to the phenotype of Dlk1 deficiency previously described in a null mouse model (23). In addition, patients with Temple syndrome may develop obesity, early onset type 2 diabetes and hyperlipidemia as young adults (26)(27)(28).…”

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Famsupporting

confidence: 83%

“…(23), who performed DLK1 sequencing analysis in 60 patients with CPP or history of precocious menarche. Three distinct frameshift mutations in the exon 5 of DLK1 were identified in five patients from three unrelated families (p.Gly199Alafs*11, p.Val271Cysfs*14 and p.Pro160Leufs*50) (23).…”

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Fammentioning

confidence: 99%

“…To investigate the effect of mutations on DLK1 production, serum DLK1 levels were measured in the affected family members (mutated DLK1 patients) and in controls, using an available soluble DLK1 enzymelinked immunosorbent assay (ELISA) (22,23). Serum DLK1 concentrations were undetectable in all tested affected individuals.…”

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Fammentioning

confidence: 99%

“…Another clinical aspect demonstrated by Gomes and cols. (23) was the presence of polycystic ovarian syndrome (PCOS) in two out of 10 adult women evaluated with DLK1 mutations. It is postulated that a neuroendocrine component may participate in PCOS physiopathology with increased GnRH pulse frequency leading to increased LH production over FSH production.…”

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Fammentioning

confidence: 99%

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Pioneering studies on monogenic central precocious puberty

Canton¹,

Seraphim²,

Brito³

et al. 2019

Archives of Endocrinology and Metabolism

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Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism.

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Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Famsupporting

confidence: 83%

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Fammentioning

confidence: 99%

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Fammentioning

confidence: 99%

Section: Inactivating Mutations In Imprinted Gene Dlk1 Leading To Fammentioning

confidence: 99%

See 2 more Smart Citations

Pioneering studies on monogenic central precocious puberty

Canton¹,

Seraphim²,

Brito³

et al. 2019

Archives of Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

“…Also, in the case of humans, a number of gene mutations have been associated with the precocious onset of puberty. For instance, mutations in Makorin Ring Finger Protein 3 ( MKRN3 ) and DLK1 gene have been reported to be associated with precocious puberty (Gomes et al, ; Yi et al, ). While going through the history of such cases, one must recognize that unless testis has matured during mid to late juvenile phase, onset of hypothalamic pulse generator prepubertally would never manifest through precocious puberty at testicular levels.…”

Section: Induction Of Precocious Puberty During Juvenile Periodmentioning

confidence: 99%

Pubertal orchestration of hormones and testis in primates

Bhattacharya

Sharma

Majumdar

2019

Molecular Reproduction Devel

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The term “Puberty”, socially known as “Adolescence” is the transitional period from juvenile life to adulthood with functional maturation of gonads and genital organs. In this process, some remarkable developmental changes occur in morphology, physiology, and behavior leading to reproductive competence. Despite sufficient levels of gonadotropins (luteinizing hormone [LH] and follicle‐stimulating hormone [FSH]), robust spermatogenesis is not initiated during infancy in primates due to the immaturity of testicular Sertoli cells. Recent studies suggest that developmental competence augmenting functional activities of receptors for androgen and FSH is acquired by Sertoli cells somewhere during the prolonged hypo‐gonadotropic juvenile period. This juvenile phase is terminated with the re‐awakening of hypothalamic Kisspeptin/Neurokinin B/Dynorphin neurons which induce the release of the gonadotropin‐releasing hormone leading to reactivation of the hypothalamo‐pituitary‐testicular axis at puberty. During this period of pubertal development, FSH and LH facilitate further maturation of testicular cells (Sertoli cells and Leydig cells) triggering robust differentiation of the spermatogonial cells, ensuing the spermatogenic onset. This review aims to precisely address the evolving concepts of the pubertal regulation of hormone production with the corresponding cooperation of testicular cells for the initiation of robust spermatogenesis, which can be truly called “testicular puberty.”

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Chinese familial central precocious puberty with hyperuricemia due to recurrent DLK1 mutation: Case report and review of the literature

Yuan¹,

Zhang²,

Liu³

et al. 2022

Molec Gen & Gen Med

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The beginning of puberty is influenced by many factors, among which genetic factors are the most prominent (Aguirre & Eugster, 2018). The genetic contribution to pubertal timing is supported by the strong correlation between the ages that children and their parents begin puberty. Twin studies demonstrated a higher concordance of the timing of development of secondary sexual characteristics, including menarche in girls, in monozygotic compared to dizygotic twins, which also provides the basis for gene regulation of puberty onset (Dvornyk & Waqar

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DLK1 Is a Novel Link Between Reproduction and Metabolism

Cited by 81 publications

References 30 publications

Pioneering studies on monogenic central precocious puberty

Pioneering studies on monogenic central precocious puberty

Pubertal orchestration of hormones and testis in primates

Chinese familial central precocious puberty with hyperuricemia due to recurrent DLK1 mutation: Case report and review of the literature

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