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.

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.

scholarly journals Evolutionary Conservation of MKRN3 and Other Makorins and Their Roles in Puberty Initiation and Endocrine Functions

2019 ◽  
Vol 37 (04) ◽  
pp. 166-173 ◽  
Author(s):  
Lydie Naulé ◽  
Ursula B. Kaiser
Keyword(s):  
Wide Spectrum ◽  
Pubertal Timing ◽  
Pubertal Development ◽  
Protein Structures ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Evolutionary Conservation ◽  
Loss Of Function ◽  
Underlying Mechanisms

AbstractPuberty is a critical period of development regulated by genetic, nutritional, and environmental factors. The role of makorin ring finger protein 3 (MKRN3) in the regulation of pubertal timing was revealed when loss-of-function mutations were identified in patients with central precocious puberty (CPP). To date, MKRN3 mutations are the most common known genetic cause of CPP. MKRN3 is a member of the makorin family of ubiquitin ligases, together with MKRN1 and MKRN2. The Mkrn genes have been identified in both vertebrates and invertebrates and show high evolutionary conservation of their gene and protein structures. While the existence of Mkrn orthologues in a wide spectrum of species suggests a vital cellular role of the makorins, their role in puberty initiation and endocrine functions is just beginning to be investigated. In this review, we discuss recent studies that have shown the involvement of Mkrn3 and other makorins in the regulation of pubertal development and other endocrine functions, including metabolism and fertility, as well as their underlying mechanisms of action.

scholarly journals Ring Finger Protein 149 Is an E3 Ubiquitin Ligase Active on Wild-type v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

2012 ◽  
Vol 287 (28) ◽  
pp. 24017-24025 ◽  
Author(s):  
Seung-Woo Hong ◽  
Dong-Hoon Jin ◽  
Jae-Sik Shin ◽  
Jai-Hee Moon ◽  
Young-Soon Na ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Wild Type ◽  
Viral Oncogene ◽  
Finger Protein ◽  
Type V ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

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 Diffusion-mediated HEI10 coarsening can explain meiotic crossover positioning in Arabidopsis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chris Morgan ◽  
John A. Fozard ◽  
Matthew Hartley ◽  
Ian R. Henderson ◽  
Kirsten Bomblies ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Ring Finger ◽  
Super Resolution ◽  
Ring Finger Protein ◽  
Wild Type ◽  
Crossover Interference ◽  
Finger Protein ◽  
Meiotic Crossover ◽  
Mechanistic Basis

AbstractIn most organisms, the number and distribution of crossovers that occur during meiosis are tightly controlled. All chromosomes must receive at least one ‘obligatory crossover’ and crossovers are prevented from occurring near one another by ‘crossover interference’. However, the mechanistic basis of this phenomenon of crossover interference has remained mostly mysterious. Using quantitative super-resolution cytogenetics and mathematical modelling, we investigate crossover positioning in the Arabidopsis thaliana wild-type, an over-expressor of the conserved E3 ligase HEI10, and a hei10 heterozygous line. We show that crossover positions can be explained by a predictive, diffusion-mediated coarsening model, in which large, approximately evenly-spaced HEI10 foci grow at the expense of smaller, closely-spaced clusters. We propose this coarsening process explains many aspects of Arabidopsis crossover positioning, including crossover interference. Consistent with this model, we also demonstrate that crossover positioning can be predictably modified in vivo simply by altering HEI10 dosage, with higher and lower dosage leading to weaker and stronger crossover interference, respectively. As HEI10 is a conserved member of the RING finger protein family that functions in the interference-sensitive pathway for crossover formation, we anticipate that similar mechanisms may regulate crossover positioning in diverse eukaryotes.

scholarly journals RING Finger Protein 11 (RNF11) modulates dopamine release in Drosophila

2020 ◽  
Author(s):  
Eve Privman Champaloux ◽  
Nathan Donelson ◽  
Poojan Pyakurel ◽  
Danielle Wolin ◽  
Leah Ostendorf ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Dopamine Release ◽  
Ring Finger ◽  
Mrna Levels ◽  
Ring Finger Protein ◽  
Fast Scan Cyclic Voltammetry ◽  
Short Intervals ◽  
Finger Protein ◽  
D2 Antagonist

AbstractRecent work indicates a role for RING finger protein 11 (RNF11) in Parkinson disease (PD) pathology, which involves the loss of dopaminergic neurons. However, the role of RNF11 in regulating dopamine neurotransmission has not been studied. In this work, we tested the effect of RNF11 RNAi knockdown or overexpression on stimulated dopamine release in the larval Drosophila central nervous system. Dopamine release was stimulated using optogenetics and monitored in real-time using fast-scan cyclic voltammetry at an electrode implanted in an isolated ventral nerve cord. RNF11 knockdown doubled dopamine release, but there was no decrease in dopamine from RNF11 overexpression. RNF11 knockdown did not significantly increase stimulated serotonin or octopamine release, indicating the effect is dopamine specific. Dopamine clearance was also changed, as RNF11 RNAi flies had a higher Vmax and RNF11 overexpressing flies had a lower Vmax than control flies. RNF11 RNAi flies had increased mRNA levels of dopamine transporter (DAT) in RNF11, confirming changes in DAT. In RNF11 RNAi flies, release was maintained better for stimulations repeated at short intervals, indicating increases in the recycled releasable pool of dopamine. Nisoxetine, a DAT inhibitor, and flupenthixol, a D2 antagonist, did not affect RNF11 RNAi or overexpressing flies differently than control. Thus, RNF11 knockdown causes early changes in dopamine neurotransmission, and this is the first work to demonstrate that RNF11 affects both dopamine release and uptake. RNF11 expression decreases in human dopaminergic neurons during PD, and that decrease may be protective by increasing dopamine neurotransmission in the surviving dopaminergic neurons.

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.

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.

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