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The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis

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Nillni, Eduardo A., Vaslet, Charles, Harris, Mark, Hollenberg, Anthony, Bjørbæk, Christian, Flier, Jeffrey S.·2000·Journal of Biological Chemistry

Abstract

The hypothalamic-pituitary-thyroid axis is down-regulated during starvation, and falling levels of leptin are a critical signal for this adaptation, acting to suppress preprothyrotropin-releasing hormone (prepro-TRH) mRNA expression in the paraventricular nucleus of the hypothalamus. This study addresses the mechanism for this regulation, using primary cultures of fetal rat hypothalamic neurons as a model system. Leptin dose-dependently stimulated a 10-fold increase in pro-TRH biosynthesis, with a maximum response at 10 nm. TRH release was quantified using immunoprecipitation, followed by isoelectric focusing gel electrophoresis and specific TRH radioimmunoassay. Leptin stimulated TRH release by 7-fold. Immunocytochemistry revealed that a substantial population of cells expressed TRH or leptin receptors and that 8-13% of those expressing leptin receptors coexpressed TRH. Leptin produced a 5-fold induction of luciferase activity in CV-1 cells transfected with a TRH promoter and the long form of the leptin receptor cDNA. Although the above data are consistent with a direct ability of leptin to promote TRH biosynthesis through actions on TRH neurons, addition of alpha-melanocyte-stimulating hormone produced a 3.5-fold increase in TRH biosynthesis and release, whereas neuropeptide Y treatment suppressed pro-TRH biosynthesis approximately 3-fold. Furthermore, the melanocortin-4 receptor antagonist SHU9119 partially inhibited leptin-stimulated TRH release from the neuronal culture. Consequently, our data suggest that leptin regulates the TRH neurons through both direct and indirect pathways.

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Metadata

Authors
Nillni, E. A., Vaslet, C., Harris, M., Hollenberg, A., Bjørbæk, C., & Flier, J. S.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-11
Volume
275
Issue
46
Pages
36124-36133
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2014508988
Cited by
209
References
16
FWCI
3.30
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis. https://app.cochat.ai/papers/10.1074/jbc.m003549200
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Nillni, E. A., Vaslet, C., Harris, M., Hollenberg, A., Bjørbæk, C., & Flier, J. S. (2000). Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m003549200

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