| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 30, 2003
Accepted on January 26, 2004
Thyroid Unit and Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA 02215
* To whom correspondence should be addressed. E-mail: thollenb{at}bidmc.harvard.edu.
The regulation of TSH-releasing hormone (TRH) gene expression in the paraventricular nucleus of the hypothalamus (PVH) by leptin is critical for normal function of the thyroid axis in rodents and humans. The TRH neuron in the PVH expresses both leptin and melanocortin-4 receptors (MC4-R) suggesting that both signaling systems may regulate TRH gene expression in vivo. Indeed, the TRH promoter responds to both of these signaling pathways in cell culture through identified cis-acting elements which include signal transducer and activator of transcription 3 (STAT3) and cAMP-response element binding protein (CREB) binding sites that mediate leptin and melanocortin responses respectively. To determine if leptin signaling can directly target the TRH promoter in vivo we developed a chromatin immunoprecipitation (ChIP) assay to use on leptin treated animals. After a single injection of leptin in fasting animals we could detect a significant increase in TRH gene expression in the PVH that correlated well with the induction of phosphorylated-STAT3 in the hypothalamus. Furthermore, using a STAT3 antibody we could immunoprecipitate the STAT-binding site containing regions of both the TRH promoter and the promoter of the suppressor of cytokine signaling-3 (SOCS-3) gene, another well-defined target of leptin action. In contrast, upstream regions of these promoters that lack STAT sites were not precipitated. Taken together these experiments demonstrate that STAT3 mediates the transcriptional effects of leptin in vivo and that the TRH promoter is a likely direct site of leptin action. In addition, these experiments demonstrate that ChIP can be used to characterize leptin-signaling in vivo.
This article has been cited by other articles:
 |
|
 |
|
  B. E. Levin Neurotrophism and energy homeostasis: perfect together Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R988 - R991. [Full Text] [PDF]
|
|
|
|
 |
|
 D C Ferguson, Z Caffall, and M Hoenig Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats J. Endocrinol., August 1, 2007; 194(2): 267 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ortega, N. Pannacciulli, C. Bogardus, and J. Krakoff Plasma concentrations of free triiodothyronine predict weight change in euthyroid persons Am. J. Clinical Nutrition, February 1, 2007; 85(2): 440 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Boelen, J Kwakkel, X G Vos, W M Wiersinga, and E Fliers Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor {beta}2 mRNA expression in mice. J. Endocrinol., August 1, 2006; 190(2): 537 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Perello, R. C. Stuart, and E. A. Nillni The Role of Intracerebroventricular Administration of Leptin in the Stimulation of Prothyrotropin Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus Endocrinology, July 1, 2006; 147(7): 3296 - 3306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fekete, P. S. Singru, E. Sanchez, S. Sarkar, M. A. Christoffolete, R. S. Riberio, W. M. Rand, C. H. Emerson, A. C. Bianco, and R. M. Lechan Differential Effects of Central Leptin, Insulin, or Glucose Administration during Fasting on the Hypothalamic-Pituitary-Thyroid Axis and Feeding-Related Neurons in the Arcuate Nucleus Endocrinology, January 1, 2006; 147(1): 520 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. McMinn, S.-M. Liu, H. Liu, I. Dragatsis, P. Dietrich, T. Ludwig, C. N. Boozer, and S. C. Chua Jr. Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E403 - E411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Guillemin Hypothalamic hormones a.k.a. hypothalamic releasing factors J. Endocrinol., January 1, 2005; 184(1): 11 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Bates, T. A. Dundon, M. Seifert, M. Carlson, E. Maratos-Flier, and M. G. Myers Jr LRb-STAT3 Signaling Is Required for the Neuroendocrine Regulation of Energy Expenditure by Leptin Diabetes, December 1, 2004; 53(12): 3067 - 3073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Tulipano, A V Vergoni, D Soldi, E E Muller, and D Cocchi Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant rats fed a high-fat diet J. Endocrinol., November 1, 2004; 183(2): 289 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Joseph-Bravo Hypophysiotropic Thyrotropin-Releasing Hormone Neurons as Transducers of Energy Homeostasis Endocrinology, November 1, 2004; 145(11): 4813 - 4815. [Full Text] [PDF]
|
|
|
|
|
|
C. Fekete, D. L. Marks, S. Sarkar, C. H. Emerson, W. M. Rand, R. D. Cone, and R. M. Lechan Effect of Agouti-Related Protein in Regulation of the Hypothalamic-Pituitary-Thyroid Axis in the Melanocortin 4 Receptor Knockout Mouse Endocrinology, November 1, 2004; 145(11): 4816 - 4821. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
