Farmacoriflessioni
Resistenza e ipersensibilità ai corticosteroidi. Dalla clinica alle basi molecolari: andata e ritorno
RESISTANCE AND HYPERSENSITIVITY TO STEROIDS
ILENIA DRIGO1, ALESSIA SACCARI2, COSETTA BACCHIN1, FIORA BARTOLI2, EGIDIO BARBI2, FLAVIA CESCHIN3, ALESSANDRO VENTURA2, GIULIANA DECORTI1
1Dipartimento di Scienze Biomediche, Università di Trieste
2Clinica Pediatrica, Dipartimento di Scienze della Riproduzione e dello Sviluppo, IRCCS “Burlo Garofolo”, Università di Trieste
3Pediatra di famiglia, Pordenone
Aprile 2006 - pagg. 241 -247
Abstract
Steroids are among the drugs of most common use in paediatric practice. This widespread use does not usually correspond to a thorough knowledge of the mechanisms underlying steroid pharmacology, especially of the steroid resistance and hypersensitivity. This paper reviews the molecular mechanisms underlying steroid resistance and hypersensitivity and reports a few related clinical cases which may be encountered in the every day clinical practice.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
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5. Shahidi H, Vottero A, Stratakis CA, et al. Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia. Biochem Biophys Res Commun 1999;254(3): 559-65.
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8. De Lange P, Segeren CM, Koper JW, et al. Expression in hematological malignancies of a glucocorticoid receptor splice variant that augments glucocorticoid receptor-mediated effects in transfected cells. Cancer Res 2001; 61(10):3937-41.
9. DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol 2002;81(2): 103-22.
10. Bronnegard M, Boos J, Marcus C, McGuire J, Werner S, Gustafsson JA. Expression of hsp90 beta messenger ribonucleic acid in patients with familial glucocorticoid resistance: correlation to receptor status. J Steroid Biochem Mol Biol 1995;52(4):345-9.
11. Kojika S, Sugita K, Inukai T, et al. Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins. Leukemia 1996; 10(6):994-9.
12. Bourgeois S, Gruol DJ, Newby RF, Rajah FM. Expression of an mdr gene is associated with a new form of resistance to dexamethasone- induced apoptosis. Mol Endocrinol 1993; 7(7):840-51.
13. Karl M, Lamberts SW, Detera-Wadleigh SD, et al. Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. J Clin Endocrinol Metab 1993;76(3):683-9.
14. Malchoff DM, Brufsky A, Reardon G, et al. A mutation of the glucocorticoid receptor in primary cortisol resistance. J Clin Invest 1993; 91(5):1918-25.
15. Ruiz M, Lind U, Gafvels M, et al. Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance. Clin Endocrinol (Oxf) 2001;55(3):363-71.
16. Kino T, Stauber RH, Resau JH, Pavlakis GN, Chrousos GP. Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: importance of the ligand-binding domain for intracellular GR trafficking. J Clin Endocrinol Metab 2001;86(11):5600-8.
17. Smoak KA, Cidlowski JA . Mechanisms of glucocorticoid receptor signaling during inflammation. Mech Ageing Dev 2004;125(10- 11):697-706.
18. Yanovski JA, Miller KD, Kino T, et al. Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab 1999; 84(6):1925-31.
19. Huizenga NA, Koper JW, De Lange P, et al. A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 1998;83(1):144-51.
2. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids: new mechanisms for old drugs. N Engl J Med 2005;353(16):1711- 23.
3. Buttgereit F, Burmester GR, Lipworth BJ. Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet 2005;365(9461): 801-3.
4. Karl M, Lamberts SW, Koper JW, et al. Cushing’s disease preceded by generalized glucocorticoid resistance: clinical consequences of a novel, dominant-negative glucocorticoid receptor mutation. Proc Assoc Am Physicians 1996;108(4):296-307.
5. Shahidi H, Vottero A, Stratakis CA, et al. Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia. Biochem Biophys Res Commun 1999;254(3): 559-65.
6. Oakley RH, Jewell CM, Yudt MR, Bofetiado DM, Cidlowski JA. The dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of action. J Biol Chem 1999;274(39):27857-66.
7. Lind U, Greenidge P, Gustafsson JA, Wright AP, Carlstedt-Duke J. Valine 571 functions as a regional organizer in programming the glucocorticoid receptor for differential binding of glucocorticoids and mineralocorticoids. J Biol Chem 1999;274(26):18515-23.
8. De Lange P, Segeren CM, Koper JW, et al. Expression in hematological malignancies of a glucocorticoid receptor splice variant that augments glucocorticoid receptor-mediated effects in transfected cells. Cancer Res 2001; 61(10):3937-41.
9. DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol 2002;81(2): 103-22.
10. Bronnegard M, Boos J, Marcus C, McGuire J, Werner S, Gustafsson JA. Expression of hsp90 beta messenger ribonucleic acid in patients with familial glucocorticoid resistance: correlation to receptor status. J Steroid Biochem Mol Biol 1995;52(4):345-9.
11. Kojika S, Sugita K, Inukai T, et al. Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins. Leukemia 1996; 10(6):994-9.
12. Bourgeois S, Gruol DJ, Newby RF, Rajah FM. Expression of an mdr gene is associated with a new form of resistance to dexamethasone- induced apoptosis. Mol Endocrinol 1993; 7(7):840-51.
13. Karl M, Lamberts SW, Detera-Wadleigh SD, et al. Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. J Clin Endocrinol Metab 1993;76(3):683-9.
14. Malchoff DM, Brufsky A, Reardon G, et al. A mutation of the glucocorticoid receptor in primary cortisol resistance. J Clin Invest 1993; 91(5):1918-25.
15. Ruiz M, Lind U, Gafvels M, et al. Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance. Clin Endocrinol (Oxf) 2001;55(3):363-71.
16. Kino T, Stauber RH, Resau JH, Pavlakis GN, Chrousos GP. Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: importance of the ligand-binding domain for intracellular GR trafficking. J Clin Endocrinol Metab 2001;86(11):5600-8.
17. Smoak KA, Cidlowski JA . Mechanisms of glucocorticoid receptor signaling during inflammation. Mech Ageing Dev 2004;125(10- 11):697-706.
18. Yanovski JA, Miller KD, Kino T, et al. Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab 1999; 84(6):1925-31.
19. Huizenga NA, Koper JW, De Lange P, et al. A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 1998;83(1):144-51.
Corrispondenza: a_saccari@libero.it