Mutation analysis of the LH receptor gene in Leydig cell adenoma and hyperplasia and functional and biochemical studies of activating mutations of the LH receptor gene

Journal of Clinical Endocrinology and Metabolism

Volumn 96, Issue 7, 2011, Pages

  Boot, Annemieke M ^a   Lumbroso, Serge ^b,c   Verhoef Post, Miriam ^d   Richter Unruh, Annette ^e   Looijenga, Leendert H J ^d   Funaro, Ada ^f   Beishuizen, Auke ^g   Van Marle, André ^d   Drop, Stenvert L S ^g   Themmen, Axel P N ^d  

^a UNIVERSITY OF GRONINGEN   (Netherlands)

^b NÎMES UNIVERSITY HOSPITAL   (France)

^c UNIV MONTPELLIER   (France)

^d ERASMUS MEDICAL CENTER   (Netherlands)

^e UNIVERSITY HOSPITAL ESSEN   (Germany)

^f Center for Molecular Biotechnology   (Italy)

^g SOPHIA CHILDREN S HOSPITAL   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CHORIONIC GONADOTROPIN; CYCLIC AMP; DNA; GONADOTROPIN; INOSITOL PHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3;

ARTICLE; CARCINOGENESIS; CELL MEMBRANE; CELLULAR DISTRIBUTION; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; ENDOSOME; GENETIC ASSOCIATION; GONADAL DISEASE; GONADOTROPIN INDEPENDENT PRECOCIOUS PUBERTY; HUMAN; HUMAN CELL; HUMAN TISSUE; INTERNALIZATION; LEYDIG CELL ADENOMA; LEYDIG CELL HYPERPLASIA; LUTEINIZING HORMONE RECEPTOR GENE; MALE; MOLECULAR PATHOLOGY; MUTANT; MUTATIONAL ANALYSIS; PRECOCIOUS PUBERTY; PRESCHOOL CHILD; PRIORITY JOURNAL; RECEPTOR GENE; RECEPTOR OCCUPANCY; SCHOOL CHILD; SIGNAL TRANSDUCTION; SOMATIC MUTATION; TESTIS DISEASE; TESTIS TUMOR; TESTOTOXICOSIS; WILD TYPE;

ADENOMA; CHILD; CHILD, PRESCHOOL; DNA MUTATIONAL ANALYSIS; HUMANS; HYPERPLASIA; LEYDIG CELLS; MALE; MUTATION; PUBERTY, PRECOCIOUS; RECEPTORS, LH; TESTICULAR NEOPLASMS;

EID: 79960108125     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2010-3031     Document Type: Article

References (28)

1. Themmen APN, Huhtaniemi IT 2000 Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 21:551-583
2. Wu SM, Leschek EW, Rennert OM, Chan WY 2000 Luteinizing hormone receptor mutations in disorders of sexual development and cancer. Front Biosci 5:D343-D352
3. Kremer H, Martens JW, van Reen M, Verhoef-Post M, Wit JM, Otten BJ, Drop SL, Delemarre-van de Waal HA, Pombo-Arias M, De Luca F, Potau N, Buckler JM, Jansen M, Parks JS, Latif HA, Moll GW, Epping W, Saggese G, Mariman EC, Themmen AP, Brunner HG 1999 A limited repertoire of mutations of the luteinizing hormone (LH) receptor gene in familial and sporadic patients with male LH-independent precocious puberty. J Clin Endocrinol Metab 84: 1136-1140 (Pubitemid 29138255)
4. Themmen AP 2005 An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms. Reproduction 130:263-274 (Pubitemid 41320751)
5. Sangkhathat S, Kanngurn S, Jaruratanasirikul S, Tubtawee T, Chaiyapan W, Patrapinyokul S, Chiengkriwate P 2010 Peripheral precocious puberty in a male caused by Leydig cell adenoma harboring a somatic mutation of the LHR gene: report of a case. J Med Assoc Thai 93:1093-1097
6. Liu G, Duranteau L, Carel JC, Monroe J, Doyle DA, Shenker A 1999 Leydig cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor.NEngl JMed341:1731-1736
7. Canto P, Söderlund D, Ramón G, Nishimura E, Méndez JP 2002 Mutational analysis of the luteinizing hormone receptor gene in two individuals with Leydig cell tumors. Am J Med Genet 108:148-152
8. Richter-Unruh A, Wessels HT, Menken U, Bergmann M, Schmittmann- Ohters K, Schaper J, Tappeser S, Hauffa BP 2002 Male LH independent sexual precocity in a 3.5 year old boy caused by a somatic activating mutation of the LH receptor in a Leydig cell tumor. J Clin Endocrinol Metab 87:1052-1056 (Pubitemid 36121064)
9. Richter-Unruh A, Jorch N, Wessels HT, Weber EA, Hauffa BP 2002 Venous sampling can be crucial in identifying the testicular origin of idiopathic male luteinising hormone-independent sexual precocity. Eur J Pediatr 161:668-671 (Pubitemid 35435540)
10. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S 1998 A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58: 5248-5257 (Pubitemid 28521189)
11. Looijenga LH, Gillis AJ, Verkerk AJ, van Putten WL, Oosterhuis JW 1999 Heterogeneous X inactivation in trophoblastic cells of human full-term female placentas. Am J Hum Genet 64:1445-1452 (Pubitemid 30468765)
12. de Jong J, Stoop H, Gillis AJ, Hersmus R, van Gurp RJ, van de Geijn GJ, van Drunen E, Beverloo HB, Schneider DT, Sherlock JK, Baeten J, Kitazawa S, van Zoelen EJ, van Roozendaal K, Oosterhuis JW, Looijenga LH 2008 Further characterization of the first seminoma cell line TCam-2. Genes Chromosomes Cancer 47:185-196 (Pubitemid 351162849)
13. Leschek EW, Chan WY, Diamond DA, Kaefer M, Jones J, Barnes KM, Cutler Jr GB 2001 Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty. J Pediatr 138:949-951 (Pubitemid 32545611)
14. Martens JW, Lumbroso S, Verhoef-Post M, Georget V, Richter- Unruh A, Szarras-Czapnik M, Romer TE, Brunner HG, Themmen AP, Sultan Ch 2002 Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency. J Clin Endocrinol Metab 87:2506-2513
15. Bakker RA, Casarosa P, Timmerman H, Smit MJ, Leurs R 2004 Constitutively active Gq/11-coupled receptors enable signaling by co-expressed G(i/o)-coupled receptors. J BiolChem279:5152-5161 (Pubitemid 38220532)
16. Song KS, Li Shengwen, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP 1996 Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains. J Biol Chem 271:9690-9697
17. Simons K, Toomre D 2000 Lipid rafts and signal transduction. Nat Rev Mol Cell Biol [Erratum (2001) 2:216) 1:31-39
18. Carver LA, Schnitzer JE 2003 Caveolae: mining little caves for new cancer targets. Nat Rev Cancer 3:571-581 (Pubitemid 37328829)
19. Martin MM, Wu SM, Martin AL, Rennert OM, Chan WY 1998 Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor. Eur J Endocrinol 139:101-106 (Pubitemid 28351243)
20. Sangkuhl K, Schulz A, Schultz G, Schöneberg T 2002 Structural requirements for mutational lutropin/choriogonadotropin receptor activation. J Biol Chem 277:47748-47755 (Pubitemid 36159299)
21. Angelova K, Fanelli F, Puett D 2008 Contributions of intracellular loops 2 and 3 of the lutropin receptor in Gs coupling. Mol Endocrinol 22:126-138
22. Kosugi S, Mori T, Shenker A 1996 The role of Asp578 in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor. J Biol Chem 271:31813-31817 (Pubitemid 26422200)
23. Laue L, Chan WY, Hsueh AJ, Kudo M, Hsu SY, Wu SM, Blomberg L, Cutler Jr GB 1995 Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in fa- milial male-limited precocious puberty. Proc Natl Acad Sci USA 92:1906-1910
24. Boikos SA, Stratakis CA 2007 Molecular genetics of the cAMP-dependent protein kinase pathway and of sporadic pituitary tumorigenesis. Hum Mol Genet 16:R80-R87 (Pubitemid 47241846)
25. Neumann S, Krause G, Chey S, Paschke R 2001 A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation. Mol Endocrinol 15: 1294-1305 (Pubitemid 32703478)
26. Tao YX, Mizrachi D, Segaloff DL 2002 Chimeras of the rat and human FSH receptors (FSHRs) identify residues that permit or suppress transmembrane 6 mutation-induced constitutive activation of the FSHR via rearrangements of hydrophobic interactions between helices 6 and 7. Mol Endocrinol 16:1881-1892 (Pubitemid 34828094)
27. Hirakawa T, Ascoli M 2003 A constitutively active somatic mutation of the human lutropin receptor found in Leydig cell tumors activates the same families of G proteins as germ line mutations associated with Leydig cell hyperplasia. Endocrinology 144:3872-3878 (Pubitemid 37088741)
28. Williams TM, Lisanti MP 2005 Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol 288:C494-C506 (Pubitemid 40229478)