Influência do treinamento físico sobre parâmetros do eixo hipotálamo-pituitária-adrenal de ratos administrados com dexametasona.

 

J. Rodrigo Pauli*

José Leme

Daniel Crespilho

M. Alice Mello

Gustavo Rogatto

Eliete Luciano

 

Universidade Estadual Paulista, Campus de Rio Claro, Instituto de Biociências, Departamento de Educação Física, Brasil.

 

Resumo

O objetivo do presente estudo foi verificar os efeitos do exercício físico agudo e crônico sobre o eixo hipotálamo-pituitária-adrenal de ratos administrados com dexametasona. Ratos Wistar jovens foram divididos em quatro grupos: controle sedentário (CS), controle treinado (CT), dexametasona sedentário (DxS) e dexametasona treinado (DxT). O protocolo de treinamento consistiu de natação 1 hora/dia, 5 dias/semana, durante 10 semanas, suportando uma sobrecarga relativa a 5% do seu peso corporal. A dexametasona foi administrada 5 dias/semana (2µg/dia diluída em 150µl de NaCl - 0,9%). Antes do sacrifício os ratos receberam insulina subcutânea para o cálculo da remoção máxima de glicose. No final do período experimental amostras de sangue foram obtidas para determinação da glicose e hormônio adrenocorticotrófico (ACTH) séricos. Amostras do músculo gastrocnêmio, da glândula adrenal e tecido adiposo epididimal foram utilizadas para determinação do peso, teor de glicogênio e ácido ascórbico, respectivamente. Nossos resultados indicam que a exposição crônica a dexametasona está associada com diminuição da sensitividade à insulina. O tratamento com dexametasona diminuiu a secreção de ACTH em resposta ao exercício agudo, mostrando diferença no funcionamento do eixo CRH-ACTH-adrenal entre os grupos estudados. Em conclusão, o exercício pode preponderar sobre o feedback negativo da dexametasona na ativação do eixo hipotálamo-pituitária-adrenal.

Palavras-chave: treinamento físico, dexametasona, resistência à insulina, eixo hipotálamo-pituitária-adrenal.

 

ABSTRACT

Influence of physical training on hypothalamo-pituitary-adrenal axis parameters of rates administered with dexametasone.

The aim of present study was to investigate the influence of acute and chronic physical exercise on the hypothalamo-pituitary-adrenal axis in Wistar rats administered with dexamethasone. Young Wistar rats were divided into four groups: sedentary control (CS), sedentary dexamethasone (DxS), trained control (CT) and trained dexamethasone (DxT). Training protocol consisted of swimming 1h/day, 5 days/week, during 10 weeks, supporting a load of 5% of their body weight. Dexamethasone was administered 5 times for week (2µg/day in 150µl 0,9% NaCl). Before sacrifying the rats each received a subcutaneous insulin to calculate the maximum decreased in blood glucose. Venous blood samples were obtained at the end of the experimental period to determine serum glucose and ACTH. Gastrocnemius, adrenal and adipose epididimal tissues’ samples were used to determine weight, glycogen and ascorbic acid concentration, respectively. Data suggests that chronic exposure to dexamethasone was associated with decreased insulin sensitivity. The dexametasona treatment decreased ACTH release in response to acute exercise, showing marked differences in the functioning of the CRH-ACTH-adrenal axis between groups of rats. In conclusion, exercise can override the dexamethasone negative feedback of hypothalamo-pituitary-adrenal axis activation in rats.

Key Words: physical training, dexamethasone, insulin resistance, hypothalamo-pituitary-adrenal axis.

 

 

Texto completo disponível apenas em PDF.

Full text only in PDF format.

 

 

BIBLIOGRAFIA

1. Severino C, Brizzi P, Solinas A, Secchi G, Maioli M, Tonolo G. (2002). Low-dose dexamethasone in the rat: a model to study insulin resistance. American Journal of Physiology 283: E367-373.        [ Links ]

2. Stojanovska L, Rosella G, Proietto J. (1990) Evolution of dexametasone-induced insulin resistance in rats. American Journal of Physiology 258: E748-756.        [ Links ]

3. Schneiter P, Tappy L. (1998). Kinetics of dexamethasone-induced alterations of glucose metabolism in health humans. American Journal of Physiology 275: E806-E813.         [ Links ]

4. Kahn BB, Flier JS. (2000). Obesity and insulin resistance. The Journal of Clinical Investigation 106 (4): 473-481.        [ Links ]

5. Hochberg Z.; Pacak K.; Chorousos G.P. (2003). Endocrine withdrawal syndromes. Endocrine Reviews 24 (4): 523-538.        [ Links ]

6. Wittert GA, Stewart DE, Graves MP, Ellis MJ, Evans MJ, Wells JE, Donald RA, Espiner EA. (1991). Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man. Clinical Endocrinology 35: 311-317.        [ Links ]

7. Inder WJ, Hellemans J, Swanney MP, Prickett TCR, Donald RA. (1998). Prolonged exercise increases peripheral plasma ACTH, CRH, and AVP in male athletes. Journal of Applied Physiology 85 (3): 835-841.        [ Links ]

8. Deuster PA, Petrides JS, Singh A, Lucci EB, Chrousos GP, Gold PW. (1998). High intensity exercise promotes escape of adrenocorticotropin and cortisol from suppression by dexamethasone: sexually dimorphic responses. Journal of Clinical Endocrinology and Metabolism 83: 3332-3338.        [ Links ]

9. Azevedo JRM (1994). Determinação de parâmetros bioquímicos em ratos sedentários e treinados após exercício agudo de natação. Tese de Doutorado. Departamento de Fisiologia e Biofísica, Universidade Estadual de Campinas, Campinas.        [ Links ]

10. Lundbaek K (1962). Intravenous glucose tolerance as a tool in definition an diagnosis of diabetes mellitus. British Medical Journal 3: 1057-1063.        [ Links ]

11. Henry R.J.; Cannon D.C.; Wilkeman J. (1974). Clinical Chemistry, principles and techniques. New York: Ed. Harper and Harper Row Publishes.        [ Links ]

12. Dubois B, Gilles KA, Hamilton JK, Rebers PA. (1956) Colorimetric method for determination of sugar and related substances. Analytical Chemistry 28: 350-356.        [ Links ]

13. Mindlin RL, Butler AM. (1938). The  determination of ascorbic acid in plasma. A micromethod. Journal of Biological Chemistry 122: 673-686.        [ Links ]

14. Bosscher K, Berghe WV, Haegeman G. (2003). The interplay between the glucocorticoid receptor and nuclear factor-kB or activator protein-1: molecular mechanisms for gene repression. Endocrine Reviews 24 (4): 488-522.        [ Links ]

15. Francischi RP, Pereira LO, Lancha Júnior AH. (2001). Exercício, comportamento alimentar e obesidade: revisão dos efeitos sobre a composição corporal e parâmetros metabólicos. Revista Paulista de Educação Física 15 (2): 117-140.        [ Links ]

16. Baker CW, Brownell KD. (2003). Atividade física e manutenção da perda de peso: mecanismos fisiológicos e psicológicos. In: C. Bouchard Atividade Física e Obesidade. São Paulo: Ed. Manole.        [ Links ]

17. Ciolac EM, Guimarães GV. (2004). Exercício físico e síndrome metabólica. Revista Brasileira de Medicina do Esporte 10 (4): 319-324.        [ Links ]

18. Mensink M, Blaak EE, Vidal H, De Bruin TWA, Glatz JFC, Saris WHM. (2003). Lifestyle changes and lipid metabolism gene expression and protein content in skeletal muscle of subjects with impaired glucose tolerance. Diabetologia 46: 1082-1089.        [ Links ]

19. Tounian P, Schneiter P, Henry S, Delarue J, Tappy L. (1997) Effects of dexamethasone on hepatic glucose production and fructose metabolism in healthy humans. American Journal of Physiology 273 (2): E315-E320.        [ Links ]

20. Carvalho CRO, Saad MJA. (1998). Resistência à insulina induzida por glicocorticóides: investigação de mecanismos moleculares. Arquivos Brasileiros de Endocrinologia e Metabologia 42 (1): 13-21.        [ Links ]

21. Fairchild TJ, Armstrong AA, Rao A, Liu H, Lawrence S, Fournier PA. (2003). Glycogen synthesis in muscle fibers during active recovery from intense exercise. Medicine and Science in Sports and Exercise 35 (4): 595-602.        [ Links ]

22. Tappy L, Randin D, Vollenweider P, Vollenweider L, Paquot N, Scherrer U, Scheneiter P, Nicod P, Jéquier E. (1994). Mechanisms of dexamethasone-induced insulin resistance in health humans. Journal of Clinical Endocrinology and Metabolism 79: 1063-1069.        [ Links ]

23. Sakoda H, Ogihara T, Anai M, Funaki M, Inukai K, KatagiriI H, Fukushima Y, Onishi Y, Ono H, Fujishiro M, Kikuchi M, Oka Y, Asano T. (2000). Dexametasona-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than signal transduction. Diabetes 49: 1700-1708.        [ Links ]

24. Luciano E, Carneiro EM, Carvalho CRO, Carvalheira JBC, Perez SB, Reis MAB, Saad MJA, Boschero AC, Velloso, LA. (2002). Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-Kinase/ Akt-1 pathway. European Journal of Endocrinology 147: 149-157.        [ Links ]

25. KunitomiI M, Takahashi K, Wada J, Suzuki H, Miyatake N, Ogawa S, Ohta S, Sugimoto H, Shikata K, Makino H. (2000). Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold. Diabetes Research and Clinical Practice 50: 109-115.        [ Links ]

26. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, Mccartney JS, Kraus WE. (2004). Effect of the volume and intensity of exercise training on insulin sensitivity. Journal of Applied Physiology 96: 101-106.        [ Links ]

27. Tabata I, Atomi Y, Mutoh Y, Miyashita M. (1990). Effect of physical training on the responses of serum adrenocorticotropic hormone during prolonged exhausting exercise. European Journal of Applied Physiology 61 (3-4): 188-192.        [ Links ]

28. Heitkamp HCH, Schultz H, Röcker K, Dickhuth HH. (1998). Endurance training in females: changes in b-endorphin and ACTH.  International Journal of Sports Medicine 19: 260-264.        [ Links ]

29. Viru M, Litvinova L, Smirnova T, Viru A. (1994). Glucocorticoids in metabolic control during exercise: glycogen metabolism. Journal Sports Med Phys Fitness 34: (4): 377-382.        [ Links ]

30. Lima JG, Nobrega LHC, Nobrega MLC, Rodrigues Jr AB, Pereira AFF. (2002). Supressão hipotálomo-hipófise-adrenal e risco de insuficiência adrenal secundária devido ao uso de dexametasona nasal. Arquivos Brasileiros de Endocrinologia & Metabologia 46 (2): 193-196.        [ Links ]

31. Junqueira LC, Carneiro J. (1995). Histologia básica. Rio de Janeiro: Ed. Guanabara Koogan.        [ Links ]

32. Kjaer RM. (1998). Adrenal medulla and exercise training. European Journal of Applied Physiology 77:195-199.        [ Links ]

33. Walker CD, Scribner KA, Stern JS, Dallman MF. (1992). Obese Zucker (fa/fa) rats exhibit normal target sensitivity to corticosterone and increased drive to adrenocorticotropin  during diurnal trough. Endocrinology 131: 2629-2637.        [ Links ]

34. Perhonen M, Takala T, Huttunen P, Leppaluoto J. (1995). Stress hormones after prolonged physical training in normo-and hipobaric conditions in rats. Journal of Sports Medicine 16 (2): 73-77.        [ Links ]

35. Pauli JR, Silva ASR, Voltarelli FA, Ferreira L, Santhiago V, Romero CEM, Machado CEP, De Almeida Leme JAC, Gomes RJ, Osares AR, Luciano E.  (2003). Efeitos do treinamento físico em água moderadamente fria sobre os parâmetros fisiológicos de ratos durante o exercício de natação. Revista Logos 11: 78-83.        [ Links ]

36. Kraemer WJ, Fleck S, Callister R, Shealey M, Dudley M, Maresh CM, Cruthirds C, Murray T, Falkel JE. (1989). Training responses of plasma beta-endorphin, adrenocorticotropin, and cortisol. Medicine and Science in Sports and Exercise 21 (2): 146-153.        [ Links ]

37. Lac G, Marquet P, Chassain AP, Galen FX. (1999). Dexamethasone in resting and exercising men. II. Effects on adrenocortical hormones. Journal of Applied Physiology 87 (1): 183-188.        [ Links ]

38. Petrides JS, Mueller GP, Kalogeros KT, Chrousos GP, Gold PW, Deuster PA. (1994). Exercise-induced activation of the hypothalamic-pituitary-adrenal axis: marked differences in the sensitivity to glucocorticoid suppression. Journal of Clinical Endocrinology and Metabolism 79: 377-383.        [ Links ]

39. Petrides JS, Gold PW, Mueller GP, Singh A, Stratakis C, Chrousos GP, Deuster PA. (1997). Marked differences in functioning of the hypothalamic-pituitary-adrenal axis between groups of men. Journal of Applied Physiology 82(6): 1979-1988.        [ Links ]

40. Deuster PA, Petrides JS, Singh A, Chrousos GP, Poth M. (2000). Endocrine response to high-intensity exercise: dose-dependent effects of dexamethasone. Journal of Clinical Endocrinology and Metabolism 85 (3): 1066-1073.        [ Links ]

41. Martignoni E, Appenzeller O, Nappi RE, Sances G, Costa A, Nappi G. (1997). The effects of physical exercise at high altitude on adrenocortical function in humans. Functional Neurology, 12 (6): 339-344.        [ Links ]

 

 

CORRESPONDÊNCIA

* José Rodrigo Pauli

Rua XV de Novembro, 1701, centro

13400-370  Piracicaba, S.P.

BRASIL

rodrigosere@yahoo.com.br