Horm Metab Res 2008; 40(12): 842-847
DOI: 10.1055/s-0028-1086024
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Downregulation of Melanocortin-4 Receptor during Refeeding and its Modulation by Adrenalectomy in Rats

C. M. R. Germano 1 , 2 , M. de Castro 1 , R. Rorato 3 , D. B. Costa 3 , J. Antunes-Rodrigues 3 , C. F. Elias 4 , L. L. K. Elias 3
  • 1Department of Internal Medicine, School of Medicine of Ribeirao Preto, Sao Paulo, Brazil
  • 2Department of Medicine, Federal University of Sao Carlos, Sao Carlos, Brazil
  • 3Department of Physiology, School of Medicine of Ribeirao Preto, Sao Paulo, Brazil
  • 4Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
Further Information

Publication History

received 20.12.2007

accepted 11.06.2008

Publication Date:
22 September 2008 (online)

Abstract

Melanocortin system and corticotropin releasing hormone (CRH) are implicated in the control of feeding behavior. Besides its anorexigenic effect on food intake, CRH is one of the most important regulators of hypothalamic-pituitary-adrenal (HPA) axis activity. Therefore, there could be an interplay between HPA axis activity and melanocortin system. We investigated the expression of melanocortin-4 receptor (MC4-R) mRNA in the hypothalamus of rats after 14 days of food restriction or after a fasting-refeeding regimen, in sham or adrenalectomized rats. Male Wistar rats were subjected to free access to food or food ingestion restricted for 2 h a day (8–10  AM) during 14 d, when plasma corticosterone, ACTH, insulin, leptin concentrations, and MC4-R mRNA expression were determined before and after refeeding. Another set of rats was fasted for 48 h, followed by refeeding during 2 or 4 h on the seventh day after adrenalectomy (ADX) or sham surgery. On the day of the experiment, rats were anesthetized and perfused and the brain processed for MC4-R mRNA by in situ hybridization. Long-term reduction of food intake, either secondary to food restriction or adrenalectomy, reduced body weight gain and also leptin and insulin plasma concentrations. Food ingestion reduced MC4-R expression in the paraventricular nucleus in naive rats subjected to food restriction and also in sham rats fasted for 48 h. However, after ADX, MC4-R expression was not changed by refeeding. In conclusion, the present data indicate that MC4-R expression is downregulated by food ingestion and this response could be modulated by glucocorticoid withdrawal.

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Correspondence

L. L. K. Elias

Department of Physiology

School of Medicine of Ribeirao Preto

Avenida Bandeirantes, 3900

14049-900 Ribeirao Preto

Sao Paulo

Brazil

Phone: +55/16/3602 30 57

Fax: +55/16/3633 00 17

Email: llelias@fmrp.usp.br

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