ArticleThe Journal of clinical investigation2004
Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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
41 citing papers in PubMed, 95 citations in OpenAlex.
- Neurotensin via Type I Receptor Modulates the Endotoxemia Induced Oxido-Inflammatory Stress on the Sympathetic Adrenomedullary System of Mice Regulating NF-κβ/Nor-Epinephrine Pathway.Cell biochemistry and biophysics · 2025Article
- The role of thyroid function in female and male infertility: a narrative review.Journal of endocrinological investigation · 2023Review
- MANF in POMC Neurons Promotes Brown Adipose Tissue Thermogenesis and Protects Against Diet-Induced Obesity.Diabetes · 2022Article
- Modulation of PC1/3 activity by a rare double-site homozygous mutation.Frontiers in pediatrics · 2022Article
- Insulin synthesized in the paraventricular nucleus of the hypothalamus regulates pituitary growth hormone production.JCI insight · 2020Article
- Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- GEOFFREY HARRIS PRIZE LECTURE 2018: Novel pathways regulating neuroendocrine function, energy homeostasis and metabolism in humans.European journal of endocrinology · 2019Review
- Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis.Molecular metabolism · 2018Article
- Review
- B Lymphocytes Express Pomc mRNA, Processing Enzymes and β-Endorphin in Painful Inflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Article
- The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.The Journal of biological chemistry · 2016Article
- Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.Endocrinology · 2015Article
- CREB/TRH pathway in the central nervous system regulates energy expenditure in response to deprivation of an essential amino acid.International journal of obesity (2005) · 2015Article
- The role of leptin in regulating bone metabolism.Metabolism: clinical and experimental · 2015Review
- Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism.Metabolism: clinical and experimental · 2015Review
- Minireview: Central Sirt1 regulates energy balance via the melanocortin system and alternate pathways.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.Endocrinology · 2014Article
- Leptin signaling regulates hypothalamic expression of nescient helix-loop-helix 2 (Nhlh2) through signal transducer and activator 3 (Stat3).Molecular and cellular endocrinology · 2014Article
- Morphine treatment selectively regulates expression of rat pituitary POMC and the prohormone convertases PC1/3 and PC2.Peptides · 2013Article
- Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort.Gastroenterology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Regulation of energy balance by leptin involves regulation of several neuropeptides, including thyrotropin-releasing hormone (TRH). Synthesized from a larger inactive precursor, its maturation requires proteolytic cleavage by prohormone convertases 1 and 2 (PC1 and PC2). Since this maturation in response to leptin requires prohormone processing, we hypothesized that leptin might regulate hypothalamic PC1 and PC2 expression, ultimately leading to coordinated processing of prohormones into mature peptides. Using hypothalamic neurons, we found that leptin stimulated PC1 and PC2 mRNA and protein expression and also increased PC1 and PC2 promoter activities in transfected 293T cells. Starvation of rats, leading to low serum leptin levels, decreased PC1 and PC2 gene and protein expression in the paraventricular nucleus (PVN) of the hypothalamus. Exogenous administration of leptin to fasted animals restored PC1 levels in the median eminence (ME) and the PVN to approximately the level found in fed control animals. Consistent with this regulation of PCs in the PVN, concentrations of TRH in the PVN and ME were substantially reduced in the fasted animals relative to the fed animals, and leptin reversed this decrease. Further analysis showed that proteolytic cleavage of pro-thyrotropin-releasing hormone (proTRH) at known PC cleavage sites was reduced by fasting and increased in animals given leptin. Combined, these findings suggest that leptin-dependent stimulation of hypothalamic TRH expression involves both activation of trh transcription and stimulation of PC1 and PC2 expression, which lead to enhanced processing of proTRH into mature TRH.
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Registered trials
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