Dataset Information

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing "Yin" and Purging "Fire" Traditional Chinese Medicine Mixture in a Rat Model.

ABSTRACT: The present study aims to investigate the effects of the nourishing "Yin" and purging "Fire" Traditional Chinese Medicine (TCM) herb mixture on precocious puberty and TCM may act through hypothalamic Lin28/let7 pathway expression in the precocious puberty model rats. Meanwhile, to confirm the relationship between Lin28/let7 pathway and puberty by overexpression Lin28a, in the first part of this study, female rats were randomly allocated into untreated controls, the precocious puberty (PP) model group, the PP control group, and the PP + TCM group. Rats on postnatal day 5 were injected danazol to establish the PP model. From days 15 to 35, the rats in the TCM group were given the TCM twice daily. Vaginal opening, sex-related hormones, and body and reproductive organ weights were measured, and the expressions of hypothalamic Lin28a and Lin28b mRNA and let7a and let7b miRNA were detected. In addition, in the second part, the effects of overexpression of Lin28a on the vaginal opening time were evaluated. In the two parts of the study, we found that, at the onset of puberty, a decrease in ovary weight, an increase in the serum levels of luteinizing hormone and progesterone, and increased expression levels of hypothalamic Lin28b mRNA were observed in the PP + TCM group compared to the PP model group. The vaginal opening time was significantly delayed upon overexpression of Lin28a. Above all, the mechanism by which the TCM treats precocious puberty is thus likely to be associated with inhibition of the hypothalamic Lin28/let7 signaling pathway and our findings provide in-depth insight into the relationship between the overexpression of Lin28a gene in the hypothalamus and the onset of puberty.

SUBMITTER: He Y

PROVIDER: S-EPMC6038664 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing "Yin" and Purging "Fire" Traditional Chinese Medicine Mixture in a Rat Model.

He Yuanyuan Y Han Xinghui X Sun Wen W Yu Jian J Tamadon Amin A

Evidence-based complementary and alternative medicine : eCAM 20180626

The present study aims to investigate the effects of the nourishing "Yin" and purging "Fire" Traditional Chinese Medicine (TCM) herb mixture on precocious puberty and TCM may act through hypothalamic Lin28/let7 pathway expression in the precocious puberty model rats. Meanwhile, to confirm the relationship between Lin28/let7 pathway and puberty by overexpression <i>Lin28a,</i> in the first part of this study, female rats were randomly allocated into untreated controls, the precocious puberty (PP) ...[more]

PMID: 30046338

Similar Datasets

Project description:BackgroundIn 90% cases of girls and 25-60% cases of boys the cause of gonadotropin-dependent precocious puberty (PP) is unclear. Up to 25-27.5% of gonadotropin-dependent PP cases are monogenic and suggest autosomal-dominant inheritance with incomplete sex-dependent penetrance. To date, mutations in genes KISS1, KISS1R, MKRN3, DLK1 have been described as causal variants leading to precocious hypothalamic-pituitary axis activation in childhood. Genetic testing in patients with hereditary forms of PP can expand our knowledge of underlying molecular mechanisms of the disease and it is also necessary for genetic counselling.AimTo study clinical features and genetic characteristics of patients with idiopathic gonadotropin-dependent precocious puberty.Materials and methodsA group of patients with idiopathic gonadotropin-dependent precocious puberty and positive family history (early or precocious puberty) was examined. Laboratory and instrumental diagnostic tests, full-exome sequencing (NGS, next-generation sequencing) were provided for all patients.ResultsThe study included 30 patients (29 girls, 1 boy) with idiopathic gonadotropin-dependent precocious puberty. The median of patients age at the time of the examination was 7,2 years [6,5; 7,7]. Positive family history presented in all cases: in 40% of patients on father's side, in 37% - on mother's side, in 23% of patients PP was diagnosed in siblings. The fullexome sequencing was conducted to 21 patients: in 61,9% of cases (95% CI [40;79]) nucleotide variants were identified in genes, associated with gonadotropin-dependent precocious puberty. MKRN3 gene defect was detected in most cases (77% cases (95% CI [49; 92]), which consistent with international data on its highest prevalence in the monogenic forms of PP. In 23% of cases (95% CI [7; 50]) nucleotide variants were identified in other candidate genes associated with neuroontogenesis and neuroendocrine regulation mechanisms of hypothalamic-pituitary axis.ConclusionOur study confirms that detailed family history data in children with PP provides a rational approach to molecular-genetic testing. Data of inheritance pattern and clinical manifestations will simplify the diagnosis of hereditary forms of disease and enhance genetic counselling of families, followed by timely examination and administration of pathogenetic therapy.

Project description:BackgroundRecent studies demonstrated that changes in DNA methylation (DNAm) and inactivation of two imprinted genes (MKRN3 and DLK1) alter the onset of female puberty. We aimed to investigate the association of DNAm profiling with the timing of human puberty analyzing the genome-wide DNAm patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (CPP) and 33 healthy girls (15 pre- and 18 post-pubertal). For this purpose, we performed comparisons between the groups: pre- versus post-pubertal, CPP versus pre-pubertal, and CPP versus post-pubertal.ResultsAnalyzing the methylome changes associated with normal puberty, we identified 120 differentially methylated regions (DMRs) when comparing pre- and post-pubertal healthy girls. Most of these DMRs were hypermethylated in the pubertal group (99%) and located on the X chromosome (74%). Only one genomic region, containing the promoter of ZFP57, was hypomethylated in the pubertal group. ZFP57 is a transcriptional repressor required for both methylation and imprinting of multiple genomic loci. ZFP57 expression in the hypothalamus of female rhesus monkeys increased during peripubertal development, suggesting enhanced repression of downstream ZFP57 target genes. Fourteen other zinc finger (ZNF) genes were related to the hypermethylated DMRs at normal puberty. Analyzing the methylome changes associated with CPP, we demonstrated that the patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Forty-eight ZNF genes were identified as having hypermethylated CpG sites in CPP.ConclusionMethylome profiling of girls at normal and precocious puberty revealed a widespread pattern of DNA hypermethylation, indicating that the pubertal process in humans is associated with specific changes in epigenetically driven regulatory control. Moreover, changes in methylation of several ZNF genes appear to be a distinct epigenetic modification underlying the initiation of human puberty.

Dataset Information

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing "Yin" and Purging "Fire" Traditional Chinese Medicine Mixture in a Rat Model.

Publications

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing "Yin" and Purging "Fire" Traditional Chinese Medicine Mixture in a Rat Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets