MKRN3 Levels in Girls with Central Precocious Puberty during GnRHa Treatment: A Longitudinal Study

2018 ◽  
Vol 90 (3) ◽  
pp. 190-195 ◽  
Author(s):  
Anna Grandone ◽  
Grazia Cirillo ◽  
Marcella Sasso ◽  
Gianluca Tornese ◽  
Caterina Luongo ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Serum Levels ◽  
Breast Development ◽  
Control Group ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
17Β Estradiol ◽  
Puberty Onset

Background: Recently, mutations of makorin RING finger protein 3 (MKRN3) have been identified in familial central precocious puberty (CPP). Serum levels of this protein decline before the pubertal onset in healthy girls and boys and are lower in patients with CPP compared to prepubertal matched pairs. The aim of our study was to investigate longitudinal changes in circulating MKRN3 levels in patients with CPP before and during GnRH analogs (GnRHa) treatment. Methods: We performed a longitudinal prospective study. We enrolled 15 patients with CPP aged 7.2 years (range: 2–8) with age at breast development onset < 8 years and 12 control girls matched for the time from puberty onset (mean age 11.8 ± 1.2 years). Serum values of MKRN3, gonadotropins, and 17β-estradiol were evaluated before and during treatment with GnRHa (at 6 and 12 months). The MKRN3 gene was genotyped in CPP patients. In the girls from the control group, only basal levels were analyzed. Results: No MKRN3 mutations were found among CPP patients. MKRN3 levels declined significantly from baseline to 6 months of GnRHa treatment (p = 0.0007) and from 6 to 12 months of treatment (p = 0.003); MKRN3 levels at 6 months were significantly lower than in the control girls (p < 0.0001). Conclusions: We showed that girls with CPP had a decline in peripheral levels of MKRN3 during GnRHa treatment. Our data suggest a suppression of MKRN3 by continuous pharmacological administration of GnRHa.

Serum Makorin ring finger protein 3 values for predicting Central precocious puberty in girls

2019 ◽  
Vol 35 (8) ◽  
pp. 732-736 ◽  
Author(s):  
Hwal Rim Jeong ◽  
Hye Jin Lee ◽  
Yeong Suk Shim ◽  
Min Jae Kang ◽  
Seung Yang ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Ring Finger Protein ◽  
Finger Protein

scholarly journals 202 Central precocious puberty in dizygotic twin sisters caused by mutation in the makorin RING finger protein 3 gene

2021 ◽  
Author(s):  
Marija Požgaj Šepec ◽  
Lavinia La Grasta Sabolić ◽  
Magdalena Avbelj Stefanija ◽  
Jernej Kovač ◽  
Gordana Stipančić
Keyword(s):  
Precocious Puberty ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Dizygotic Twin ◽  
Ring Finger Protein ◽  
Finger Protein

scholarly journals Evaluation of Serum Makorin Ring Finger Protein 3 (MKRN3) Levels in Girls With Idiopathic Central Precocious Puberty and Premature Thelarche

2020 ◽  
pp. 127-133 ◽  
Author(s):  
W. GE ◽  
H.-L. WANG ◽  
H.-J. SHAO ◽  
H.-W. LIU ◽  
R.-Y. XU
Keyword(s):  
Precocious Puberty ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Healthy Controls ◽  
Diagnostic Biomarker ◽  
Ring Finger Protein ◽  
Premature Thelarche ◽  
Finger Protein ◽  
Idiopathic Central Precocious Puberty ◽  
Diagnostic Criterion

This study aims to investigate serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty (ICPP) and premature thelarche (PT), in order to determine whether circulating MKRN3 level is associated with ICPP and PT. A total of 90 girls were enrolled in the study. 30 age-matched girls were allocated for each group (ICPP, PT and healthy controls [HC], respectively). The base LH (B-LH) and E2 levels were higher in ICPP girls than those in HC and PT girls. The peak LH (P-LH) levels and P-LH/P-FSH values were obviously higher in ICPP girls than those in PT girls, while higher peak FSH (P-FSH) levels were detected in PT girls when compared to those in ICPP girls. Kisspeptin levels were lower in HC girls than those in ICPP and PT girls. MKRN3 levels were the highest in HC girls among the three groups. There were relatively strong negative correlations among MKRN3, kisspeptin and P-LH/P-FSH. Circulating MKRN3 can have an important role in the onset of ICPP and PT. However, this should not be used as an independent diagnostic criterion for diagnosing ICPP or differentiating ICPP from PT, but should be used only as an adjunctive diagnostic biomarker.

scholarly journals A case of familial central precocious puberty caused by a novel mutation in the makorin RING finger protein 3 gene

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Anna Grandone ◽  
Grazia Cantelmi ◽  
Grazia Cirillo ◽  
Pierluigi Marzuillo ◽  
Caterina Luongo ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Novel Mutation ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Ring Finger Protein ◽  
Finger Protein

scholarly journals The Peripubertal Decline in Makorin Ring Finger Protein 3 Expression is Independent of Leptin Action

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Stephanie A Roberts ◽  
Ana Paula Abreu ◽  
Victor M Navarro ◽  
Joy N Liang ◽  
Caroline A Maguire ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pubertal Development ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Mrna Levels ◽  
Ring Finger Protein ◽  
Loss Of Function ◽  
Wild Type ◽  
Finger Protein ◽  
Significant Difference

Abstract A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of Makorin Ring Finger Protein 3 (MKRN3), in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic Mkrn3 mRNA levels observed in mice during pubertal development. We first used a leptin-deficient (ob/ob) mouse model. Mkrn3 mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in ob/ob mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on Mkrn3 expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in Mkrn3 expression levels in either the MBH or POA. In summary, regulation of Mkrn3 expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in Mkrn3 at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.

scholarly journals Genotype-phenotype correlations in central precocious puberty caused by MKRN3 mutations

2020 ◽  
Author(s):  
Carlos Eduardo Seraphim ◽  
Ana Pinheiro Machado Canton ◽  
Luciana Montenegro ◽  
Maiara Ribeiro Piovesan ◽  
Delanie B Macedo ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Genetic Defect ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Control Group ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Reproductive Axis ◽  
Time Of Presentation

Abstract Context Loss-of-function mutations of makorin RING finger protein 3 (MKRN3) are the most common monogenic cause of familial central precocious puberty (CPP). Objective To describe the clinical and hormonal features of a large cohort of patients with CPP due to MKRN3 mutations and compare the characteristics of different types of genetic defects. Patients/methods Multiethnic cohort of 716 patients with familial or idiopathic CPP screened for MKRN3 mutations using Sanger sequencing. A group of 156 Brazilian girls with idiopathic CPP (ICPP) was used as control group. Results Seventy-one patients (45 girls and 26 boys from 36 families) had 18 different loss-of-function MKRN3 mutations. Eight mutations were classified as severe (70% of patients). Among the 71 patients, first pubertal signs occurred at 6.2 ± 1.2 years in girls and 7.1 ± 1.5 years in boys. Girls with MKRN3 mutations had a shorter delay between puberty onset and first evaluation and higher FSH levels compared to ICPP. Patients with severe MKRN3 mutations had a greater bone age advancement compared to patients with missense mutations (2·3 ± 1·6 vs. 1·6 ± 1·4 years, p = 0.048), and had higher basal LH levels (2·2 ± 1·8 vs. 1·1 ± 1·1 UI/L, p=0.018) at the time of presentation. Computational protein modeling revealed that 60% of the missense mutations were predicted to cause protein destabilization. Conclusions Inherited premature activation of the reproductive axis caused by loss-of-function mutations of MKRN3 is clinically indistinct from ICPP. However, the type of genetic defect may affect bone age maturation and gonadotropin levels.

scholarly journals Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog

2007 ◽  
Vol 156 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Claudio Maffeis ◽  
Roberto Franceschi ◽  
Paolo Moghetti ◽  
Marta Camilot ◽  
Silvana Lauriola ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Serum Levels ◽  
Gnrh Analog ◽  
Therapy Discontinuation ◽  
17Β Estradiol ◽  
Therapy Withdrawal ◽  
Ghrelin Secretion

Decreased levels of ghrelin have been measured in growing children during puberty. No data are available for girls with central precocious puberty (CPP). Aims: To explore ghrelin changes before, during, and after GnRH analog treatment in girls with CPP. Subjects and methods: A sample of 20 Caucasian girls (8.08 ± 0.65 years of age) with CPP was recruited. Height and weight, bone age, LH, FSH, 17β estradiol (E2), and ghrelin were measured before starting treatment with GnRH analog, 18 months after therapy began and again 6 months after therapy discontinuation. Results: LH and E2 serum levels decreased significantly during treatment (2.45 ± 2.03 vs 0.67 ± 0.49 UI/l, P < 0.01 and 28.17 ± 9.7 vs 15 pmol/l, P < 0.01 respectively), returning to baseline levels after the discontinuation of therapy (4.75 ± 1.66 UI/l and 29.23 ± 6.99 pmol/l respectively). LH peaked following LHRH stimulation significantly (P < 0.01) decreased during treatment (24.45 ± 14.17 vs 1.3 ± 0.18 UI/l) and then increased after therapy discontinuation (12.58 ± 6.09, P < 0.01). Ghrelin decreased significantly (P < 0.05) during treatment (1849 ± 322 vs 1207 ± 637 pg/ml), and increased, though not significantly (P = 0.09) after therapy withdrawal (1567 ± 629 pg/ml). Conclusions: Contrary to what is expected in physiologic puberty, where ghrelin is progressively reduced, the prepubertal hormone milieau induced by GnRHa treatment in patients suffering from central precocious puberty (CPP) did not promote an increase in ghrelin circulating levels. Therefore, in CPP, ghrelin secretion seems to be independent from pubertal development per se. Concomitant estrogen suppression during treatment may play a potential role in the regulation of ghrelin secretion in these girls.

Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hwal Rim Jeong ◽  
Jong Seo Yoon ◽  
Hye Jin Lee ◽  
Yeong Suk Shim ◽  
Min Jae Kang ◽  
...  
Keyword(s):  
Serum Level ◽  
Precocious Puberty ◽  
Standard Deviation Score ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Loss Of Function ◽  
Early Puberty ◽  
Significant Difference

AbstractBackgroundMakorin ring finger protein 3 (MKRN3) is associated with the initiation of puberty, and loss of function mutation of MKRN3 is the most common genetic cause of central precocious puberty (CPP). A recent study reported that MKRN3 interacts with and suppresses neural pentraxin-1 precursor (NPTX1) activity via polyubiquitination during early puberty in the mouse hypothalamus.ObjectiveThis study investigated the correlation between serum NPTX1 and MKRN3 in CPP girls and predicted the potential role of NPTX1 in pubertal progression.MethodsIn this case–control study, we examined 34 girls diagnosed with CPP and 34 healthy prepubertal girls. Anthropometric and hormonal parameters were measured and serum levels of NPTX1 and MKRN3 were evaluated with commercial enzyme-linked immunosorbent assay kits.ResultsSerum MKRN3 level decreased significantly in CPP patients compared to controls (344.48 ± 333.77 and 1295.21 ± 780.80 pg/mL, respectively, p<0.001). Serum MKRN3 tended to decrease as Tanner breast stage increased. However, no significant difference was observed in serum NPTX1 levels between patients and controls (20.14 ± 31.75 ng/mL and 12.93 ± 8.28 ng/mL, respectively, p=0.248). The serum level of NPTX1 did not change significantly with the Tanner breast stage. Serum NPTX1 was correlated with the height standard deviation score (r=0.255; p<0.05), but was not correlated with serum MKRN3 level or the others. Conclusion: Although serum NPTX1 level was independent of serum MKRN3 level, the possibility they might be involved in the progression of puberty or CPP remains. Further research is needed to determine their role in the hypothalamus.

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