ArticleEndocrinology2016
Manganese-Stimulated Kisspeptin Is Mediated by the IGF-1/Akt/Mammalian Target of Rapamycin Pathway in the Prepubertal Female Rat.
Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Manganese modulates hepatocellular carcinoma cytotoxicity and doxorubicin sensitivity in a dose dependent manner.Frontiers in oncology · 2026Article
- Impact of prenatal Di(2-ethylhexyl) phthalate exposure on pubertal development in female offspring rats: A focus on ERα-Mediated IGF-1/NKB crosstalk in the hypothalamus.Scientific reports · 2025Article
- Manganese-induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation in Female Rats.Endocrinology · 2025Article
- Causal association between mTOR-dependent circulating protein levels and central precocious puberty: a Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Review
- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
- The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats.Reproductive biology and endocrinology : RB&E · 2022Article
- Childhood obesity and central precocious puberty.Frontiers in endocrinology · 2022Review
- How alcohol affects insulin-like growth factor-1's influences on the onset of puberty: A critical review.Alcoholism, clinical and experimental research · 2021Review
- Understanding the complex role of mTORC as an intracellular critical mediator of whole-body metabolism in anorexia nervosa: A mini review.Acta bio-medica : Atenei Parmensis · 2021Review
- Manganese Acts upon Insulin/IGF Receptors to Phosphorylate AKT and Increase Glucose Uptake in Huntington's Disease Cells.Molecular neurobiology · 2020Article
- Regulation of prepubertal dynorphin secretion in the medial basal hypothalamus of the female rat.Journal of neuroendocrinology · 2019Article
- Acute manganese treatment restores defective autophagic cargo loading in Huntington's disease cell lines.Human molecular genetics · 2019Article
- Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity.Neurotoxicity research · 2018Article
- A dual fluorescence reporter system for high throughput screening of effectors ofFEBS open bio · 2018Article
- Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events.Alcoholism, clinical and experimental research · 2018Article
- Phosphatidylinositol 3 kinase (PI3K) modulates manganese homeostasis and manganese-induced cell signaling in a murine striatal cell line.Neurotoxicology · 2018Article
- Regulation of Kisspeptin Synthesis and Release in the Preoptic/Anterior Hypothalamic Region of Prepubertal Female Rats: Actions of IGF-1 and Alcohol.Alcoholism, clinical and experimental research · 2018Article
- Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells.International journal of molecular sciences · 2017Article
- Influences of manganese on pubertal development.The Journal of endocrinology · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Low-dose administration of manganese chloride (MnCl2) causes release of hypothalamic LH-releasing hormone (LHRH) and advances puberty in rat. Recently, this element was shown to up-regulate mammalian target of rapamycin (mTOR), kisspeptin gene (KiSS-1), and LHRH gene expressions in the brain preoptic area (POA)/anteroventral periventricular (AVPV) nucleus. Because these genes are critical for puberty, this study was conducted to identify the upstream mechanism by which Mn activates the mTOR/KiSS-1 pathway. On day 12, immature female rats began receiving a daily supplemental dose of 10 mg/kg of MnCl2 or saline by gavage, and POA/AVPV tissues were collected on day 29 for specific protein assessments. Another experiment assessed in vitro IGF-1 release in response to Mn and assessed signal transduction pathways in the POA/AVPV region after Mn delivery into the third ventricle. Chronic Mn exposure increased (P < .05) basal expressions of mTOR and kisspeptin proteins. Mn increased protein kinase B (Akt) and Ras homolog enriched in brain, both capable of activating mTOR. Central Mn delivery increased expressions of phosphorylated IGF-1 receptor (IGF-1R) (P < .05) and Akt (P < .01) in the POA/AVPV region. The previous central delivery of JB1, an IGF-1R antagonist, blocked Mn-induced expressions of both phosphorylated IGF-1R and Akt. Downstream to Akt, centrally administered Mn increased tuberous sclerosis complex 2 (P < .05), Ras homolog enriched in brain (P < .01), mTOR (P < .05), and kisspeptin (P < .05). Finally, we observed that the early puberty induced by Mn was blocked by the administration of an mTOR inhibitor. These results suggest that Mn acts, at least in part, through the IGF-1/Akt/mTOR pathway to influence prepubertal kisspeptin and LHRH.
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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.