This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sarkar, S. Articles by Lechan, R. M. Search for Related Content PubMed PubMed Citation Articles by Sarkar, S. Articles by Lechan, R. M.

Central Administration of Neuropeptide Y Reduces -Melanocyte-Stimulating Hormone-Induced Cyclic Adenosine 5'-Monophosphate Response Element Binding Protein (CREB) Phosphorylation in Pro-Thyrotropin-Releasing Hormone Neurons and Increases CREB Phosphorylation in Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus

Tupper Research Institute and Department of Medicine (S.S., R.M.L.), Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, Tufts-New England Medical Center, and Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111

Address all correspondence and requests for reprints to: Ronald M. Lechan M.D., Ph.D., Professor of Medicine, Division of Endocrinology, Box No. 268, Tufts-New England Medical Center, 750 Washington Street, Boston, Massachusetts 02111. E-mail: rlechan{at}lifespan.org.

Neuropeptide Y (NPY) has a potent inhibitory effect on TRH gene expression in the paraventricular nucleus (PVN) and contributes to the fall in circulating thyroid hormone levels during fasting mediated by a reduction in serum leptin levels. Because -MSH activates the TRH gene by increasing the phosphorylation of CREB in the nucleus of these neurons, we raised the possibility that at least one of the mechanisms by which NPY reduces TRH mRNA in hypophysiotropic neurons is by antagonizing the ability of -MSH to phosphorylate CREB. As NPY increases CRH mRNA in the hypothalamus, we further determined whether intracerebroventricular (icv) administration of NPY regulates the phosphorylation of CREB in hypophysiotropic CRH neurons. NPY [10 µg in artificial CSF (aCSF)] was administered into the lateral ventricle icv 30 min before the icv administration of aCSF or -MSH (10 µg in aCSF), the latter in a dose previously demonstrated to increase proTRH mRNA and phosphorylate CREB in TRH neurons. By double-labeling immunocytochemistry, only few TRH neurons in the PVN contained phosphoCREB (PCREB) in animals treated only with aCSF (4 ± 0.2%) or with NPY followed by aCSF (9.7 ± 2.5), whereas -MSH-infused animals dramatically increased the percentage of TRH neurons containing PCREB (75.3 ± 6.9%). Pretreatment with NPY before -MSH infusion, however, significantly reduced the percentage of TRH neurons containing PCREB (40.8 ± 3.5%) compared with -MSH infused animals (P = 0.01). Only 12.2 ± 0.9% of CRH neurons of the medial parvocellular neurons contained PCREB nuclei in vehicle-treated animals, whereas 30 min following NPY infusion, the number of CRH neurons containing PCREB increased dramatically to 88 ± 2.9%. Whereas -MSH infusion increased the percentage of CRH neurons that contained PCREB to 56 ± 2.2% compared with control, animals pretreated with NPY further increased the number of CRH neurons colocalizing with PCREB to 87 ± 2.5%. These data demonstrate a functional interaction between NPY and -MSH in the regulation of proTRH neurons in the PVN, suggesting that NPY can antagonize -MSH induced activation of the TRH gene by interfering with melanocortin signaling at the postreceptor level, preventing the phosphorylation of CREB. In contrast, NPY infusion increases the phosphorylation of CREB in CRH neurons, indicating that NPY has independent effects on discrete populations of neurons in the PVN, presumably mediated through different signaling mechanisms.

This article has been cited by other articles:

				E. Sanchez, P. S. Singru, R. Acharya, M. Bodria, C. Fekete, A. M. Zavacki, A. C. Bianco, and R. M. Lechan Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus Endocrinology, September 1, 2008; 149(9): 4329 - 4335. [Abstract] [Full Text] [PDF]

				T. Fuzesi, G. Wittmann, Z. Liposits, R. M. Lechan, and C. Fekete Contribution of Noradrenergic and Adrenergic Cell Groups of the Brainstem and Agouti-Related Protein-Synthesizing Neurons of the Arcuate Nucleus to Neuropeptide-Y Innervation of Corticotropin-Releasing Hormone Neurons in Hypothalamic Paraventricular Nucleus of the Rat Endocrinology, November 1, 2007; 148(11): 5442 - 5450. [Abstract] [Full Text] [PDF]

				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]

				E. L. Dimitrov, M. R. DeJoseph, M. S. Brownfield, and J. H. Urban Involvement of Neuropeptide Y Y1 Receptors in the Regulation of Neuroendocrine Corticotropin-Releasing Hormone Neuronal Activity Endocrinology, August 1, 2007; 148(8): 3666 - 3673. [Abstract] [Full Text] [PDF]

				M. S. Landa, S. I. Garcia, M. L. Schuman, A. Burgueno, A. L. Alvarez, F. E. Saravia, C. Gemma, and C. J. Pirola Knocking down the diencephalic thyrotropin-releasing hormone precursor gene normalizes obesity-induced hypertension in the rat Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1388 - E1394. [Abstract] [Full Text] [PDF]

				G. van Dijk, K. de Vries, C. Nyakas, B. Buwalda, T. Adage, F. Kuipers, M. J. H. Kas, R. A. H. Adan, C. W. Wilkinson, T. E. Thiele, et al. Reduced Anorexigenic Efficacy of Leptin, But Not of the Melanocortin Receptor Agonist Melanotan-II, Predicts Diet-Induced Obesity in Rats Endocrinology, December 1, 2005; 146(12): 5247 - 5256. [Abstract] [Full Text] [PDF]

				C. D. Morrison, G. J. Morton, K. D. Niswender, R. W. Gelling, and M. W. Schwartz Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1051 - E1057. [Abstract] [Full Text] [PDF]

				S. Stanley, K. Wynne, B. McGowan, and S. Bloom Hormonal Regulation of Food Intake Physiol Rev, October 1, 2005; 85(4): 1131 - 1158. [Abstract] [Full Text] [PDF]

				K. Wynne, S. Stanley, B. McGowan, and S. Bloom Appetite control J. Endocrinol., February 1, 2005; 184(2): 291 - 318. [Abstract] [Full Text] [PDF]

				J. M. Zigman and J. K. Elmquist Minireview: From Anorexia to Obesity--The Yin and Yang of Body Weight Control Endocrinology, September 1, 2003; 144(9): 3749 - 3756. [Abstract] [Full Text] [PDF]