| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 3, 2003
Accepted on December 22, 2003
MSH and TRH and implicates prohormone convertases I and II in obesity
1 Department of Veterinary and Animal Sciences and Center for Neuroendocrine Studies, University of Massachusetts, Amherst 01003 and Division of Endocrinology, Department of Medicine, Brown Medical School, Rhode Island Hospital, Providence, RI 02903
* To whom correspondence should be addressed. E-mail: goodd{at}vasci.umass.edu.
Body weight is controlled by the activation of signal transduction pathways in both the brain and peripheral tissues. Interestingly, although many hypothalamic neuropeptides and receptors have been implicated in the regulation of body weight, the transcriptional and post-transcriptional mechanisms through which these genes are expressed in response to changes in energy balance remain unclear. Our laboratory studies a mouse in which targeted deletion of the neuronal basic helix-loop-helix transcription factor, Nhlh2, results in adult-onset obesity. The aim of this work was to use the phenotype of the Nhlh2 knockout mouse and the expression pattern of Nhlh2 to identify genes that are regulated by this transcription factor. In this paper, we show that Nhlh2 is expressed throughout the adult hypothalamus. Using dual-label in situ hybridization, we demonstrate that in the arcuate nucleus of the adult hypothalamus, Nhlh2 expression can be found in rostral pro-opiomelanocortin (POMC) neurons, while in the paraventricular nucleus, Nhlh2 is expressed in TSH-releasing hormone (TRH) neurons. In addition, we find that hypothalamic POMC-derived 
MSH in the arcuate nucleus and TRH in the paraventricular nucleus are regulated post-transcriptionally via Nhlh2-mediated control of pro-hormone convertase I and II mRNA levels. This is the first report in which regulation of body weight is linked to the action of a neuronal basic helix-loop-helix transcription factor on prohormone convertase mRNA levels. Furthermore, this work supports a direct role for transcriptional control of neuropeptide processing enzymes in the etiology of adult-onset obesity.
MSH •
adult-onset obesity •
knockout mice •
post-transcriptional regulation •
neuropeptide processing
This article has been cited by other articles:
 |
|
 |
|
  D. L. Fox and D. J. Good Nescient Helix-Loop-Helix 2 Interacts with Signal Transducer and Activator of Transcription 3 to Regulate Transcription of Prohormone Convertase 1/3 Mol. Endocrinol., June 1, 2008; 22(6): 1438 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. DeBoer, X. Zhu, P. R. Levasseur, A. Inui, Z. Hu, G. Han, W. E. Mitch, J. E. Taylor, H. A. Halem, J. Z. Dong, et al. Ghrelin Treatment of Chronic Kidney Disease: Improvements in Lean Body Mass and Cytokine Profile Endocrinology, February 1, 2008; 149(2): 827 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Pritchard and A. White Neuropeptide Processing and Its Impact on Melanocortin Pathways Endocrinology, September 1, 2007; 148(9): 4201 - 4207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Nillni Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin Endocrinology, September 1, 2007; 148(9): 4191 - 4200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks Physiol Rev, July 1, 2007; 87(3): 933 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Lloyd, S. Bohan, and N. Gekakis Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice Hum. Mol. Genet., June 1, 2006; 15(11): 1884 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. M. Creemers, L. E. Pritchard, A. Gyte, P. Le Rouzic, S. Meulemans, S. L. Wardlaw, X. Zhu, D. F. Steiner, N. Davies, D. Armstrong, et al. Agouti-Related Protein Is Posttranslationally Cleaved by Proprotein Convertase 1 to Generate Agouti-Related Protein (AGRP)83-132: Interaction between AGRP83-132 and Melanocortin Receptors Cannot Be Influenced by Syndecan-3 Endocrinology, April 1, 2006; 147(4): 1621 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 ABDOMINAL OBESITY STUDY GROUP, F. E. VON EYBEN, J. P. KROUSTRUP, J. F. LARSEN, and J. CELIS Comparison of Gene Expression in Intra-Abdominal and Subcutaneous Fat: A Study of Men with Morbid Obesity and Nonobese Men Using Microarray and Proteomics Ann. N.Y. Acad. Sci., December 1, 2004; 1030(1): 508 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zimmermann-Belsing and U. Feldt-Rasmussen Obesity: The New Worldwide Epidemic Threat to General Health and Our Complete Lack of Effective Treatment Endocrinology, April 1, 2004; 145(4): 1501 - 1502. [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 |
