This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luque, R. M. Articles by Tena-Sempere, M. Search for Related Content PubMed PubMed Citation Articles by Luque, R. M. Articles by Tena-Sempere, M.

Regulation of Hypothalamic Expression of KiSS-1 and GPR54 Genes by Metabolic Factors: Analyses Using Mouse Models and a Cell Line

Section of Endocrinology, Diabetes, and Metabolism (R.M.L., R.D.K.), Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607; Research and Development Division (R.M.L., R.D.K.), Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612; Department of Cell Biology, Physiology, and Immunology (M.T.-S.), University of Cordoba, 14004 Cordoba, Spain; and CIBER (CB06/03) Fisiopatología de la Obesidad y Nutrición (M.T.-S.), Instituto Salud Carlos III, 28029 Madrid, Spain

Address all correspondence and requests for reprints to: Manuel Tena-Sempere, Physiology Section, Department of Cell Biology, Physiology, and Immunology, University of Cordoba, Avenida Menendez Pidal, 14004 Cordoba, Spain. E-mail: fi1tesem{at}uco.es.

It is well established that reproductive function is metabolically gated. However, the mechanisms whereby energy stores and metabolic cues influence fertility are yet to be completely deciphered. Recently, the hypothalamic KiSS-1/GPR54 system has emerged as a fundamental regulator of the gonadotropic axis, which conveys the modulatory actions of sex steroids to GnRH neurons. Evidence is also mounting that KiSS-1 neurons may also represent the link between systemic metabolic signals and central control of reproduction. To further explore this possibility, we examined the impact of changes in energy status and key metabolic regulators on the hypothalamic expression of KiSS-1 and GPR54 genes, using different mouse models and the hypothalamic cell line N6. Time-course analysis of the effects of short-term fasting revealed a rapid (12- and 24-h) decline in KiSS-1 and GPR54 mRNA levels, which preceded that of GnRH (48 h). In contrast, diet-induced obesity or obesity associated with leptin deficiency (ob/ob vs. wild-type mice) failed to induce overt changes in hypothalamic expression of KiSS-1 and GPR54 genes. However, leptin infusion of ob/ob mice evoked a significant increase in KiSS-1 and GPR54 mRNA levels compared with pair-fed controls. Moreover, leptin, but not insulin or IGF-I, stimulated KiSS-1 mRNA expression in the mouse hypothalamic cell line N6. In addition, neuropeptide Y (NPY) null mice showed decreased KiSS-1 mRNA levels at the hypothalamus, whereas exposure to NPY increased expression of KiSS-1 in hypothalamic N6 cells. In sum, our present data further characterize the functional relevance and putative key mediators (such as leptin and NPY) of the metabolic regulation of the hypothalamic KiSS-1 system in the mouse.

This article has been cited by other articles:

				D. D. Belsham, L. J. Fick, P. S. Dalvi, M.-L. Centeno, J. A. Chalmers, P. K. P. Lee, Y. Wang, D. J. Drucker, and M. M. Koletar Ciliary neurotrophic factor recruitment of glucagon-like peptide-1 mediates neurogenesis, allowing immortalization of adult murine hypothalamic neurons FASEB J, December 1, 2009; 23(12): 4256 - 4265. [Abstract] [Full Text] [PDF]

				J. Roa, D. Garcia-Galiano, L. Varela, M. A. Sanchez-Garrido, R. Pineda, J. M. Castellano, F. Ruiz-Pino, M. Romero, E. Aguilar, M. Lopez, et al. The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System Endocrinology, November 1, 2009; 150(11): 5016 - 5026. [Abstract] [Full Text] [PDF]

				J. Donato Jr, R. J. Silva, L. V. Sita, S. Lee, C. Lee, S. Lacchini, J. C. Bittencourt, C. R. Franci, N. S. Canteras, and C. F. Elias The Ventral Premammillary Nucleus Links Fasting-Induced Changes in Leptin Levels and Coordinated Luteinizing Hormone Secretion J. Neurosci., April 22, 2009; 29(16): 5240 - 5250. [Abstract] [Full Text] [PDF]

				A.K. Roseweir and R.P. Millar The role of kisspeptin in the control of gonadotrophin secretion Hum. Reprod. Update, March 1, 2009; 15(2): 203 - 212. [Abstract] [Full Text] [PDF]

				J. M. Castellano, V. M. Navarro, J. Roa, R. Pineda, M. A. Sanchez-Garrido, D. Garcia-Galiano, E. Vigo, C. Dieguez, E. Aguilar, L. Pinilla, et al. Alterations in Hypothalamic KiSS-1 System in Experimental Diabetes: Early Changes and Functional Consequences Endocrinology, February 1, 2009; 150(2): 784 - 794. [Abstract] [Full Text] [PDF]

				J. K. Hiney, V. K. Srivastava, M. D. Pine, and W. L. Dees Insulin-Like Growth Factor-I Activates KiSS-1 Gene Expression in the Brain of the Prepubertal Female Rat Endocrinology, January 1, 2009; 150(1): 376 - 384. [Abstract] [Full Text] [PDF]

				T. J Greives, L. J Kriegsfeld, G. E Bentley, K. Tsutsui, and G. E Demas Recent advances in reproductive neuroendocrinology: a role for RFamide peptides in seasonal reproduction? Proc R Soc B, September 7, 2008; 275(1646): 1943 - 1951. [Abstract] [Full Text] [PDF]

				J. Roa, E. Vigo, D. Garcia-Galiano, J. M. Castellano, V. M. Navarro, R. Pineda, C. Dieguez, E. Aguilar, L. Pinilla, and M. Tena-Sempere Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1088 - E1096. [Abstract] [Full Text] [PDF]