ArticleThe Journal of clinical investigation2020
MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 92 citations in OpenAlex.
- Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.The Journal of clinical endocrinology and metabolism · 2022Trial
- Article
- Hypothalamic control of puberty: from neuronal circuits to mechanisms for its metabolic regulation.Reviews in endocrine & metabolic disorders · 2026Review
- Article
- The complete genome of the KOLF2.1J reference iPSC line.bioRxiv : the preprint server for biology · 2026Article
- Knockout of PI4-Kinase A in GnRH Neurons Causes their Prepubertal Death.bioRxiv : the preprint server for biology · 2026Article
- Divergent epigenetic profile underlie pubertal disorders in MKRN3-associated central precocious puberty and Prader-Willi syndrome: insights from a frameshift variant.World journal of pediatrics : WJP · 2026Article
- PI4-kinase A is essential for survival of the GnRH neurons.Frontiers in endocrinology · 2026Article
- Syndrome differentiation and treatment of pediatric central precocious puberty: role of the spleen-kidney axis.Frontiers in immunology · 2026Review
- Kisspeptin and neurokinin B: roles in reproductive health.Physiological reviews · 2025Review
- High-throughput transcriptome analysis reveals a developmental increase in Acvr1c which mediates epigenetic repression of the gene encoding the pubertal brake, Makorin ring finger protein 3.NAR molecular medicine · 2025Article
- Shared Pathophysiological Mechanisms and Genetic Factors in Early Menarche and Polycystic Ovary Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- A novel model of central precocious puberty disease: Paternal MKRN3 gene-modified rabbit.Animal models and experimental medicine · 2025Article
- GnRH and Cognition.Endocrinology · 2025Review
- Genetics and Epigenetics of Human Pubertal Timing: The Contribution of Genes Associated With Central Precocious Puberty.Journal of the Endocrine Society · 2025Review
- Disorders of puberty and neurodevelopment: A shared etiology?Annals of the New York Academy of Sciences · 2024Review
- MKRN3 circulating levels in girls with central precocious puberty caused by MKRN3 gene mutations.Journal of endocrinological investigation · 2024Article
- [Recent advances in the genetic etiology of central precocious puberty].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- Metabolic control of puberty: 60 years in the footsteps of Kennedy and Mitra's seminal work.Nature reviews. Endocrinology · 2024Review
- Review
Corrections and comments
- Commented on by
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The identification of loss-of-function mutations in MKRN3 in patients with central precocious puberty in association with the decrease in MKRN3 expression in the medial basal hypothalamus of mice before the initiation of reproductive maturation suggests that MKRN3 is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In the current study, we investigated the mechanism by which MKRN3 prevents premature manifestation of the pubertal process. We showed that, as in mice, MKRN3 expression is high in the hypothalamus of rats and nonhuman primates early in life, decreases as puberty approaches, and is independent of sex steroid hormones. We demonstrated that Mkrn3 is expressed in Kiss1 neurons of the mouse hypothalamic arcuate nucleus and that MKRN3 repressed promoter activity of human KISS1 and TAC3, 2 key stimulators of GnRH secretion. We further showed that MKRN3 has ubiquitinase activity, that this activity is reduced by MKRN3 mutations affecting the RING finger domain, and that these mutations compromised the ability of MKRN3 to repress KISS1 and TAC3 promoter activity. These results indicate that MKRN3 acts to prevent puberty initiation, at least in part, by repressing KISS1 and TAC3 transcription and that this action may involve an MKRN3-directed ubiquitination-mediated mechanism.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.