Tetrahydrogestrinone is an androgenic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchidectomized male rats

Endocrinology

Volumn 146, Issue 10, 2005, Pages 4472-4478

  Jasuja, R ^a,c   Catlin, D H ^b   Miller, A ^a   Chang, Y C ^b   Herbst, K L ^a   Starcevic, B ^b   Artaza, J N ^a   Singh, R ^a   Datta, G ^a   Sarkissian, A ^a   Chandsawangbhuwana, C ^d   Baker, M ^d   Bhasin, S ^a,c  

^a CHARLES R DREW UNIVERSITY OF MEDICINE AND SCIENCE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANABOLIC AGENT; ANDROGEN; ANDROGEN RECEPTOR; ANDROSTANOLONE; ANDROSTENEDIONE; FAT; FUNCTIONAL GROUP; MYOSIN HEAVY CHAIN; MYOSIN II; RECOMBINANT RECEPTOR; TESTOSTERONE ENANTATE; TETRAHYDROGESTRINONE;

ANDROGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANISOTROPY; ARTICLE; BIOSYNTHESIS; CASTRATION; CONTROLLED STUDY; DISSOCIATION CONSTANT; DOSE RESPONSE; FLUORESCENCE; HORMONE RECEPTOR INTERACTION; IN VIVO STUDY; LEVATOR ANI MUSCLE; MALE; MESENCHYME CELL; MOLECULAR MODEL; MUSCLE ATROPHY; MUSCLE DEVELOPMENT; MUSCLE GROWTH; MYOTUBE; NONHUMAN; ORCHIECTOMY; PRIORITY JOURNAL; PROSTATE; PROTEIN EXPRESSION; RAT; RECEPTOR AFFINITY; RECEPTOR UPREGULATION; SCREENING; SEMINAL VESICLE; SIGNAL TRANSDUCTION;

ANIMALS; CELL DIFFERENTIATION; CELLS, CULTURED; GESTRINONE; MALE; MESODERM; MICE; MUSCLE, SKELETAL; ORCHIECTOMY; RATS; RECEPTORS, ANDROGEN;

EID: 24944527415     PISSN: 00137227     EISSN: None     Source Type: Journal    
DOI: 10.1210/en.2005-0448     Document Type: Article

References (35)

1. Catlin DH, Sekera MH, Ahrens BD, Starcevic B, Chang Y-C, Hatton CK 2004 Tetrahydrogestrinone: discovery, synthesis, and detection in urine. Rapid Commun Mass Spectrom 18:1245-1249
2. Anabolic Steroid Control Act P.L.N. 1990, XIX:104 Stat 4851, Amended in 2004 as Anabolic Steroid Control Act of 2004, Section 102 of the Controlled Substances Act (21 U.S.C. 802)
3. Federal Drug Administration 2004 FDA warning on unapproved performance enhancer. FDA Consum 38:4
4. KondroW2003 Athletes' "designer steroid" leads to widening scandal. Lancet 362:1466
5. Ashley S 2004 Doping by design. Sci Am 290:22-23
6. Handelsman DJ 2004 Designer androgens in sport: when too much is never enough. Sci STKE 2004:pe41
7. Roy AK, Tyagi RK, Song CS, Lavrovsky Y, Ahn SC, Oh TS, Chatterjee B 2001 Androgen receptor: structural domains and functional dynamics after ligand-receptor interaction. Ann. NY Acad Sci 949:44-57
8. Jenster G, van der Korput JA, Trapman J, Brinkmann AO 1992 Functional domains of the human androgen receptor. J Steroid Biochem Mol Biol 41:671-675
9. Tan JA, Joseph DR, Quarmby VE, Lubahn DB, Sar M, French FS, Wilson EM 1988 The rat androgen receptor: primary structure, autoregulation of its messenger ribonucleic acid, and immunocytochemical localization of the receptor protein. Mol Endocrinol 2:1276-1285
10. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS 1995 Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 16:271-321
11. Gobinet J, Poujol N, Sultan C 2002 Molecular action of androgens. Mol Cell Endocrinol 198:15-24
12. Jenster G, van der Korput HA, van Vroonhoven C, van der Kwast TH, Trapman J, Brinkmann AO 1991 Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Mol Endocrinol 5:1396-1404
13. Brinkmann AO, Faber PW, van Rooij HC, Kuiper GG, Ris C, Klaassen P, van der Korput JA, Voorhorst MM, van Laar JH, Mulder E, Trapman J 1989 The human androgen receptor: domain structure, genomic organization and regulation of expression. J Steroid Biochem 34:307-310
14. Kemppainen JA, Lane MV, Sar M, Wilson EM 1992 Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. J Biol Chem 267:968-997
15. Moras D, Gronemeyer H 1998 The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol 10:384-391
16. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S 2003 Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 multipotent cells through an androgen receptor-mediated pathway. Endocrinology 144:5081-5088
17. Jasuja R, Ramaraj P, Mac RP, Singh AB, Storer TW, Artaza JA, Miller A, Singh R, Taylor WE, Lee ML, Davidson T, Sinha-Hikim I, Gonzalez-Cadavid N, Bhasin S 2005 δ-4-Androstene-3,17-dione binds androgen receptor, promotes myogenesis in vitro, and increases serum testosterone levels, fat-free mass, and muscle strength in hypogonadal men. J Clin Endocrinol Metab 90:855-863
18. Herschberger LG, Shipley EV, Meyer RK 1953 Myotrophic activity of 19-nortestosterone and other steroids determined by levator ani muscle method. Proc Soc Exper Biol Med 83:175-180
19. Krieg M, Smith K, Elvers B 1980 Androgen receptor translocation from cytosol of rat heart muscle, bulbocavernosus/levator ani muscle and prostate into heart muscle nuclei. J Steroid Biochem 13:577-587
20. Bhasin S, Fielder TJ, Peacock N, Sod-Moriah UA, Swerdloff RS 1988 Dissociating antifertility effects of GnRH-antagonist from its adverse effects on mating behavior in male rats. Am J Physiol 17:84-90
21. Ozers MS, Hill JJ, Ervin K, Wood JR, Nardulli AM, Royer CA, Gorski J 1997 Equilibrium binding of estrogen receptor using fluorescence anisotropy. Nucleic Acids Res 272:30405-30411
22. Fagart J, Wurtz JM, Souque A, Hellal-Levy C, Moras D, Rafestin-Oblin ME 1998 Antagonism in human mineralocorticoid receptor. EMBO J 17:3317-3325
23. Wolden-Hanson T, Marck BT, Smith L, MatsumotoAM1999 Cross-sectional and longitudinal analysis of age-associated changes in body composition of male Brown Norway rats: association of serum leptin levels with peripheral adiposity. J Gerontol A Biol Sci Med Sci 54:B99-B107
24. Johansen PB, Flyvbjerg A, Wilken M, Malmlöf K 2000 Comparison of methods of analysis of body composition in hypophysectomized rats treated with rat growth hormone. Growth Horm IGF Res 10:342-348
25. Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr., Weinmann R, Einspahr HM 2001 Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci USA 98:4904-4909
26. Matias PM, Donner P, Coelho R, Thomaz M, Peixoto C, Macedo S, Otto N, Joschko S, Scholz P, Wegg A, Basler S, Schafer M, Egner U, Carrondo MA 2000 Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. J Biol Chem 275:26164-26171
27. Matias PM, Carrondo MA, Coelho R, Thomaz M, Zhao XY, Wegg A, Crusius K, Egner U, Donner P 2002 Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgenindependent prostate cancer. J Med Chem 45:1439-1446
28. Williams SP, Sigler, PB 1998 Atomic structure of progesterone complexed with its receptor. Nature 393:392-396
29. McPhaul MJ 2002 Molecular defects of the androgen receptor. Recent Prog Horm Res 57:181-194
30. Taylor SM, Jones PA 1979 Multiple new phenotypes induced in 10T1/2 and 2T3 cells treated with azacytidine. Cell 17:769-779
31. Lassar AB, Paterson BM, Weintraub H 1986 Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell 47:649-656
32. Fischer L, Boland G, Tuan RS 2002 Wnt-3A enhances bone morphogenetic protein-2-mediated chondrogenesis of murine C3H10T1/2 mesenchymal cells. J Biol Chem 277:30870-30878
33. Jasuja R, Catlin DH, Herbst KL, Chang YC, Miller A, Starcevic B, Artaza JA, Singh R, Datta G, Sarkissian A, Bhasin S, Tetrahydrogestrinone (THG) binds to androgen receptor (AR) and activates AR-mediated signaling pathway. Program of the 86th Annual Meeting of The Endocrine Society, New Orleans, LA, 2004, p 122 (Abstract P122)
34. Death AK, McGrath KC, Kazlauskas R, Handelsman DJ 2004 Tetrahydrogestrinone is a potent androgen and progestin. J Clin Endocrinol Metab 89:2498-2500
35. Labrie F, Luu-The V, Calvo E, Martel C, Cloutier J, Gauthier S, Belleau P, Morissette J, Levesque MH, Labrie C 2004 Tetrahydrogestrinone induces a genomic signature typical of a potent anabolic steroid. J Endocrinol 184:427-433