This Article Full Text Full Text (PDF) 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 Beauloye, V. Articles by Thissen, J.-P. Search for Related Content PubMed PubMed Citation Articles by Beauloye, V. Articles by Thissen, J.-P.

Impairment of Liver GH Receptor Signaling by Fasting

Unité de Diabétologie et Nutrition, Université Catholique de Louvain (V.B., B.W., V.d.C., J.-P.T.), B-1200 Brussels, Belgium; Unité d’Endocrinologie Moléculaire, INSERM, U-344, Faculté de Médecine Necker-Enfants Malades (V.B., M.E.), 75730 Paris, France; Department of Cell Biology, University of Alabama (S.J.F.), Birmingham, Alabama 35294

Address all correspondence and requests for reprints to: Jean-Paul Thisssen, M.D., Ph.D., Unité de Diabétologie et Nutrition, UCL/DIAB 5474, Avenue Hippocrate 54, B-1200 Brussels, Belgium. E-mail: . thissen{at}diab.ucl.ac.be

Fasting causes a state of GH resistance responsible for low circulating IGF-I levels. To investigate whether this resistance may result from alterations in the GH signaling pathway, we determined the effects of fasting on the GH transduction pathway in rat liver. Forty-eight-hour fasted or fed male rats were injected with recombinant rat GH via the portal vein. Liver was removed 0 and 15 min after injection. Although GH stimulated Janus kinase 2 (JAK2) phosphorylation in all animals, this was severely blunted in fasted animals. Similarly, the phosphorylation of the GH receptor, although observed in both fasted and fed rats after GH injection, was markedly reduced in fasted rats. A rapid signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation was also induced in the liver of fed animals in response to GH. In contrast, in fasted rats only a slight phosphorylated STAT5 signal was observed. The inhibitory effect of fasting on these GH signaling molecules occurred without changes in their protein content. Furthermore, the impairment of the JAK-STAT pathway in fasted animals was associated with increased liver suppressor of cytokine signaling 3 mRNA levels. Although glucocorticoids, which are increased by fasting, may cause GH resistance, adrenalectomy failed to prevent alterations in the JAK-STAT pathway caused by fasting. In conclusion, the GH resistance induced by fasting is associated with impairment of the JAK-STAT signaling pathway. This might contribute to the decrease in liver IGF-I production observed in fasting.

This article has been cited by other articles:

				M. Carriquiry, W. J. Weber, C. R. Dahlen, G. C. Lamb, L. H. Baumgard, and B. A. Crooker Production response of multiparous Holstein cows treated with bovine somatotropin and fed diets enriched with n-3 or n-6 fatty acids J Dairy Sci, October 1, 2009; 92(10): 4852 - 4864. [Abstract] [Full Text] [PDF]

				E. F. Gevers, M. J. Hannah, M. J. Waters, and I. C. A. F. Robinson Regulation of Rapid Signal Transducer and Activator of Transcription-5 Phosphorylation in the Resting Cells of the Growth Plate and in the Liver by Growth Hormone and Feeding Endocrinology, August 1, 2009; 150(8): 3627 - 3636. [Abstract] [Full Text] [PDF]

				M. Shimizu, K. A. Cooper, W. W. Dickhoff, and B. R. Beckman Postprandial changes in plasma growth hormone, insulin, insulin-like growth factor (IGF)-I, and IGF-binding proteins in coho salmon fasted for varying periods Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R352 - R361. [Abstract] [Full Text] [PDF]

				M. E Picha, M. J Turano, C. K Tipsmark, and R. J Borski Regulation of endocrine and paracrine sources of Igfs and Gh receptor during compensatory growth in hybrid striped bass (Morone chrysopsxMorone saxatilis) J. Endocrinol., October 1, 2008; 199(1): 81 - 94. [Abstract] [Full Text] [PDF]

				M. Carriquiry, W. J. Weber, and B. A. Crooker Administration of Bovine Somatotropin in Early Lactation: A Meta-Analysis of Production Responses by Multiparous Holstein Cows J Dairy Sci, July 1, 2008; 91(7): 2641 - 2652. [Abstract] [Full Text] [PDF]

				M A Hyatt, G S Gopalakrishnan, J Bispham, S Gentili, I C McMillen, S M Rhind, M T Rae, C E Kyle, A N Brooks, C Jones, et al. Maternal nutrient restriction in early pregnancy programs hepatic mRNA expression of growth-related genes and liver size in adult male sheep J. Endocrinol., January 1, 2007; 192(1): 87 - 97. [Abstract] [Full Text] [PDF]

				J.-C. Gabillard, B. B. Kamangar, and N. Montserrat Coordinated regulation of the GH/IGF system genes during refeeding in rainbow trout (Oncorhynchus mykiss). J. Endocrinol., October 1, 2006; 191(1): 15 - 24. [Abstract] [Full Text] [PDF]

				J.-C. Gabillard, K. Yao, M. Vandeputte, J. Gutierrez, and P.-Y. Le Bail Differential expression of two GH receptor mRNAs following temperature change in rainbow trout (Oncorhynchus mykiss). J. Endocrinol., July 1, 2006; 190(1): 29 - 37. [Abstract] [Full Text] [PDF]

				R. P. Radcliff, B. L. McCormack, D. H. Keisler, B. A. Crooker, and M. C. Lucy Partial Feed Restriction Decreases Growth Hormone Receptor 1A mRNA Expression in Postpartum Dairy Cows J Dairy Sci, February 1, 2006; 89(2): 611 - 619. [Abstract] [Full Text] [PDF]

				B. C. Nindl, K. R. Rarick, J. W. Castellani, A. P. Tuckow, J. F. Patton, A. J. Young, and S. J. Montain Altered secretion of growth hormone and luteinizing hormone after 84 h of sustained physical exertion superimposed on caloric and sleep restriction J Appl Physiol, January 1, 2006; 100(1): 120 - 128. [Abstract] [Full Text] [PDF]

				P. Koutkia, S. Schurgin, J. Berry, J. Breu, B. S. H. Lee, A. Klibanski, and S. Grinspoon Reciprocal changes in endogenous ghrelin and growth hormone during fasting in healthy women Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E814 - E822. [Abstract] [Full Text] [PDF]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				Y. Wang, S. Eleswarapu, W. E. Beal, W. S. Swecker Jr., R. M. Akers, and H. Jiang Reduced Serum Insulin-Like Growth Factor (IGF) I Is Associated with Reduced Liver IGF-I mRNA and Liver Growth Hormone Receptor mRNA in Food-Deprived Cattle J. Nutr., August 1, 2003; 133(8): 2555 - 2560. [Abstract] [Full Text] [PDF]

				H. Norrelund, J. Frystyk, J. O. L. Jorgensen, N. Moller, J. S. Christiansen, H. Orskov, and A. Flyvbjerg The Effect of Growth Hormone on the Insulin-Like Growth Factor System during Fasting J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3292 - 3298. [Abstract] [Full Text] [PDF]

				L. Q. Hong-Brown, C. R. Brown, R. N. Cooney, R. A. Frost, and C. H. Lang Sepsis-induced muscle growth hormone resistance occurs independently of STAT5 phosphorylation Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E63 - E72. [Abstract] [Full Text] [PDF]

				F. Gu, N. Dube, J. W. Kim, A. Cheng, M. d. J. Ibarra-Sanchez, M. L. Tremblay, and Y. R. Boisclair Protein Tyrosine Phosphatase 1B Attenuates Growth Hormone-Mediated JAK2-STAT Signaling Mol. Cell. Biol., June 1, 2003; 23(11): 3753 - 3762. [Abstract] [Full Text] [PDF]

				S.-E. Kong, R. C. Baxter, and P. J. D. Delhanty Age-Dependent Regulation of the Acid-Labile Subunit in Response to Fasting-Refeeding in Rats Endocrinology, December 1, 2002; 143(12): 4505 - 4512. [Abstract] [Full Text] [PDF]

				P. Ribaux, A. Gjinovci, H. B. Sadowski, and P. B. Iynedjian Discrimination between Signaling Pathways in Regulation of Specific Gene Expression by Insulin and Growth Hormone in Hepatocytes Endocrinology, October 1, 2002; 143(10): 3766 - 3772. [Abstract] [Full Text] [PDF]

				S.-E. Kong, S. M. Firth, R. C. Baxter, and P. J. D. Delhanty Regulation of the acid-labile subunit in sustained endotoxemia Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E692 - E701. [Abstract] [Full Text] [PDF]