A novel mutation of the hGR gene causing Chrousos syndrome

European Journal of Clinical Investigation

Volumn 45, Issue 8, 2015, Pages 782-791

  Nicolaides, Nicolas C ^a,b   Geer, Eliza B ^c   Vlachakis, Dimitrios ^b   Roberts, Michael L ^a,b   Psarra, Anna Maria G ^d   Moutsatsou, Paraskevi ^a   Sertedaki, Amalia ^a,b   Kossida, Sophia ^b,e   Charmandari, Evangelia ^a,b  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b BIOMEDICAL RESEARCH FOUNDATION   (Greece)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF THESSALY   (Greece)

^e UMR 9002 CNRS UM   (France)

Author keywords

Chrousos syndrome; Glucocorticoid receptor; Glucocorticoid signalling; Mutations

Indexed keywords

ANDROSTENEDIONE; ARGININE; CORTICOTROPIN; DEXAMETHASONE; GENOMIC DNA; GLUCOCORTICOID RECEPTOR; GLUTATHIONE TRANSFERASE; HISTIDINE; HYDROCORTISONE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NUCLEAR RECEPTOR COACTIVATOR 2; NR3C1 PROTEIN, HUMAN;

ACNE; ADULT; ALOPECIA; AMINO ACID SUBSTITUTION; ANDROSTENEDIONE BLOOD LEVEL; ANXIETY; ARTICLE; BINDING AFFINITY; CASE REPORT; CHROUSOS SYNDROME; CONTROLLED STUDY; CORTICOTROPIN BLOOD LEVEL; DNA FLANKING REGION; ENDOCRINE DISEASE; EVENING DOSAGE; EXON; FATIGUE; FEMALE; GLUCOCORTICOID RECEPTOR GENE; HIRSUTISM; HORMONE SENSITIVITY; HUMAN; HUMAN CELL; HYDROCORTISONE BLOOD LEVEL; HYDROCORTISONE URINE LEVEL; HYDROGEN BOND; LIGAND BINDING; MENSTRUAL IRREGULARITY; MOLECULAR MODEL; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEOTIDE SEQUENCE; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; RECEPTOR BINDING; RECEPTOR GENE; SIGNAL TRANSDUCTION; TRANSACTIVATION; WESTERN BLOTTING; WILD TYPE; ACNE VULGARIS; ANIMAL; CHEMICAL STRUCTURE; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; DEFICIENCY; GENE EXPRESSION REGULATION; GENETICS; GENOTYPE; INBORN ERROR OF METABOLISM; MENSTRUATION DISORDER; MOLECULAR DOCKING; MUTATION; SYNDROME;

ACNE VULGARIS; ADULT; ALOPECIA; ANIMALS; ANXIETY; BLOTTING, WESTERN; CERCOPITHECUS AETHIOPS; COS CELLS; FATIGUE; FEMALE; GENE EXPRESSION REGULATION; GENOTYPE; HIRSUTISM; HUMANS; MENSTRUATION DISTURBANCES; METABOLISM, INBORN ERRORS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; MUTATION; RECEPTORS, GLUCOCORTICOID; SYNDROME;

EID: 84937405510     PISSN: 00142972     EISSN: 13652362     Source Type: Journal    
DOI: 10.1111/eci.12470     Document Type: Article

References (35)

1. Nicolaides NC, Charmandari E, Chrousos GP, Kino T. Recent advances in the molecular mechanisms determining tissue sensitivity to glucocorticoids: novel mutations, circadian rhythm and ligand-induced repression of the human glucocorticoid receptor. BMC Endocr Disord 2014;14:71.
2. Nicolaides NC, Galata Z, Kino T, Chrousos GP, Charmandari E. The human glucocorticoid receptor: molecular basis of biologic function. Steroids 2010;75:1-12.
3. Charmandari E, Kino T, Chrousos GP. Primary generalized familial and sporadic glucocorticoid resistance and hypersensitivity. Endocr Dev 2013;24:67-85.
4. Charmandari E. Primary generalized glucocorticoid resistance and hypersensitivity: the end-organ involvement in the stress response. Sci Signal 2012;5:pt5.
5. Charmandari E. Primary generalized glucocorticoid resistance and hypersensitivity. Horm Res Paediatr 2011;76:145-55.
6. Charmandari E, Kino T, Ichijo T, Chrousos GP. Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder. J Clin Endocrinol Metab 2008;93:1563-72.
7. Chrousos G. Q&A: primary generalized glucocorticoid resistance. BMC Med 2011;9:27.
8. Charmandari E, Kino T, Souvatzoglou E, Vottero A, Bhattacharyya N, Chrousos GP. Natural glucocorticoid receptor mutants causing generalized glucocorticoid resistance: molecular genotype, genetic transmission, and clinical phenotype. J Clin Endocrinol Metab 2004;89:1939-49.
9. Charmandari E, Chrousos GP, Kino T. Identification of natural human glucocorticoid receptor (hGR) mutations or polymorphisms and their functional consequences at the hormone-receptor interaction level. Methods Mol Biol 2009;590:33-60.
10. Chrousos GP, Vingerhoeds A, Brandon D, Eil C, Pugeat M, DeVroede M et al. Primary cortisol resistance in man: a glucocorticoid receptor-mediated disease. J Clin Invest 1982;69:1261-9.
11. Hurley DM, Accili D, Stratakis CA, Karl M, Vamvakopoulos N, Rorer E et al. Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest 1991;87:680-6.
12. Karl M, Lamberts SW, Detera-Wadleigh SD, Encio IJ, Stratakis CA, Hurley DM et al. Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. J Clin Endocrinol Metab 1993;76:683-9.
13. Malchoff DM, Brufsky A, Reardon G, McDermott P, Javier EC, Bergh CH et al. A mutation of the glucocorticoid receptor in primary cortisol resistance. J Clin Invest 1993;91:1918-25.
14. Karl M, Lamberts SW, Koper JW, Katz DA, Huizenga NE, Kino T 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;108:296-307.
15. 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;86:5600-8.
16. Ruiz M, Lind U, Gafvels M, Eggertsen G, Carlstedt-Duke J, Nilsson L et al. Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance. Clin Endocrinol 2001;55:363-71.
17. Charmandari E, Kino T, Ichijo T, Zachman K, Alatsatianos A, Chrousos GP. Functional characterization of the natural human glucocorticoid receptor (hGR) mutants hGRαR477H and hGRαG679S associated with generalized glucocorticoid resistance. J Clin Endocrinol Metab 2006;91:1535-43.
18. Mendonca BB, Leite MV, de Castro M, Kino T, Elias LL, Bachega TA et al. Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene. J Clin Endocrinol Metab 2002;87:1805-9.
19. Vottero A, Kino T, Combe H, Lecomte P, Chrousos GP. A novel, C-terminal dominant negative mutation of the GR causes familial glucocorticoid resistance through abnormal interactions with p160 steroid receptor coactivators. J Clin Endocrinol Metab 2002;87:2658-67.
20. Charmandari E, Raji A, Kino T, Ichijo T, Tiulpakov A, Zachman K et al. A novel point mutation in the ligand-binding domain (LBD) of the human glucocorticoid receptor (hGR) causing generalized glucocorticoid resistance: the importance of the C terminus of hGR LBD in conferring transactivational activity. J Clin Endocrinol Metab 2005;90:3696-705.
21. Charmandari E, Kino T, Ichijo T, Jubiz W, Mejia L, Zachman K et al. A novel point mutation in helix 11 of the ligand-binding domain of the human glucocorticoid receptor gene causing generalized glucocorticoid resistance. J Clin Endocrinol Metab 2007;92:3986-90.
22. McMahon SK, Pretorius CJ, Ungerer JP, Salmon NJ, Conwell LS, Pearen MA et al. Neonatal complete generalized glucocorticoid resistance and growth hormone deficiency caused by a novel homozygous mutation in Helix 12 of the ligand binding domain of the glucocorticoid receptor gene (NR3C1). J Clin Endocrinol Metab 2010;95:297-302.
23. Nader N, Bachrach BE, Hurt DE, Gajula S, Pittman A, Lescher R et al. A novel point mutation in the helix 10 of the human glucocorticoid receptor causes Generalized Glucocorticoid Resistance by disrupting the structure of the ligand-binding domain. J Clin Endocrinol Metab 2010;95:2281-5.
24. Zhu HJ, Dai YF, Wang O, Li M, Lu L, Zhao WG et al. Generalized glucocorticoid resistance accompanied with an adrenocortical adenoma and caused by a novel point mutation of human glucocorticoid receptor gene. Chin Med J 2011;124:551-5.
25. Roberts ML, Kino T, Nicolaides NC, Hurt DE, Katsantoni E, Sertedaki A et al. A novel point mutation in the DNA-binding domain (DBD) of the human glucocorticoid receptor causes primary generalized glucocorticoid resistance by disrupting the hydrophobic structure of its DBD. J Clin Endocrinol Metab 2013;98:E790-5.
26. Nicolaides NC, Roberts ML, Kino T, Braatvedt G, Hurt DE, Katsantoni E et al. A novel point mutation of the human glucocorticoid receptor gene causes primary generalized glucocorticoid resistance through impaired interaction with the LXXLL motif of the p160 coactivators: dissociation of the transactivating and transreppressive activities. J Clin Endocrinol Metab 2014;99:E902-7.
27. Biggadike K1, Bledsoe RK, Hassell AM, Kirk BE, McLay IM, Shewchuk LM et al. X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain. J Med Chem 2008;51:3349-52.
28. Molecular Operating Environment (MOE 2014.09) Montreal, Quebec, Canada: Chemical Computing Group, Inc.; Available at: http://www.chemcomp.com.
29. Hess B, Kutzner C, van der Spoel D, Lindahl E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 2008;4:435-47.
30. Van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. GROMACS: fast, flexible, and free. J Comput Chem 2005;26:1701-18.
31. Ding XF, Anderson CM, Ma H, Hong H, Uht RM, Kushner PJ et al. Nuclear receptor-binding sites of coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1): multiple motifs with different binding specificities. Mol Endocrinol 1998;12:302-13.
32. Hong H, Kohli K, Garabedian MJ, Stallcup MR. GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. Mol Cell Biol 1997;17:2735-44.
33. Hong H, Kohli K, Trivedi A, Johnson DL, Stallcup MR. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci USA 1996;93:4948-52.
34. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD et al. Crystal structure of the glucocorticoid receptor ligand-binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 2002;110:93-105.
35. Kauppi B, Jakob C, Färnegårdh M, Yang J, Ahola H, Alarcon M et al. The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism. J Biol Chem 2003;278:22748-54.