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Abstract:

We have previously demonstrated that male transgenic (TG) mice overexpressing human chorionic gonadotropin (hCG+) develop reproductive organ defects, but no tumors, in adult age. In this study, the effects of persistently elevated hCG were followed in TG males between day 5 postpartum and adulthood. Leydig cell (LC) adenomas were found in prepubertal mice, most prominently at the age of 10 days, but not in adult age. Serum testosterone concentrations were significantly increased in TG males at all ages studied. The phenotype of the prepubertal hCG+ males resembled that found in boys upon expression of constitutively activating luteinizing hormone (LH) receptor mutations. The temporal expression patterns of the fetal LC marker gene, thrombospondin 2, and those of adult LCs, hydroxysteroid dehydrogenase-6, delta5-3-beta and prostaglandin D synthase, were similar in wild-type and hCG+ males. Hence, the postnatal adenomas resemble functionally fetal LCs, and only these cells are susceptible to hCG-induced tumorigenesis. Our findings demonstrate a novel intriguing difference between the fetal and adult LC populations and provide further insight into the potential tumorigenic effects of gonadotropins. © 2005 Nature Publishing Group All rights reserved.

Registro:

Documento: Artículo
Título:Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: A study on hCG overexpressing transgenic mice
Autor:Ahtiainen, P.; Rulli, S.B.; Shariatmadari, R.; Pelliniemi, L.J.; Toppari, J.; Poutanen, M.; Huhtaniemi, I.T.
Filiación:Department of Physiology, University of Turku, FIN-20520 Turku, Finland
Turku Graduate School of Biomedical Science, University of Turku, FIN-20520 Turku, Finland
Institute of Biology and Experimental Medicine-CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Laboratory of Electron Microscopy, University of Turku, FIN-20520 Turku, Finland
Department of Pediatrics, University of Turku, FIN-20520 Turku, Finland
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom
Palabras clave:Adult Leydig cell; Fetal Leydig cell; hCG; Tumor; 3beta hydroxy delta5 steroid dehydrogenase; chorionic gonadotropin; isoenzyme; luteinizing hormone receptor; prostaglandin D synthase; testosterone; thrombospondin 2; adenoma; adulthood; age distribution; animal cell; animal experiment; animal model; animal tissue; article; cancer susceptibility; carcinogenesis; concentration (parameters); concentration response; controlled study; developmental stage; fetus; fetus cell; gender; gene overexpression; human; Leydig cell; male; marker gene; mutation; nonhuman; nucleotide sequence; perinatal period; phenotype; prepuberty; priority journal; protein expression; puerperium; testosterone blood level; transgenic mouse; wild type; 3-Hydroxysteroid Dehydrogenases; Adenoma; Animals; Chorionic Gonadotropin, beta Subunit, Human; Fetus; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Glycoprotein Hormones, alpha Subunit; Humans; Intramolecular Oxidoreductases; Leydig Cells; Male; Mice; Mice, Transgenic; Phenotype; Testis; Thrombospondins; Up-Regulation; Animalia; Mus musculus
Año:2005
Volumen:24
Número:49
Página de inicio:7301
Página de fin:7309
DOI: http://dx.doi.org/10.1038/sj.onc.1208893
Título revista:Oncogene
Título revista abreviado:Oncogene
ISSN:09509232
CODEN:ONCNE
CAS:3beta hydroxy delta5 steroid dehydrogenase, 9044-85-3; chorionic gonadotropin, 9002-61-3; prostaglandin D synthase, 65802-85-9; testosterone, 58-22-0; thrombospondin 2, 299491-48-8; 3-Hydroxysteroid Dehydrogenases, EC 1.1.-; Chorionic Gonadotropin, beta Subunit, Human; Glycoprotein Hormones, alpha Subunit; Intramolecular Oxidoreductases, EC 5.3.-; prostaglandin R2 D-isomerase, EC 5.3.99.2; thrombospondin 2; Thrombospondins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v24_n49_p7301_Ahtiainen

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Citas:

---------- APA ----------
Ahtiainen, P., Rulli, S.B., Shariatmadari, R., Pelliniemi, L.J., Toppari, J., Poutanen, M. & Huhtaniemi, I.T. (2005) . Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: A study on hCG overexpressing transgenic mice. Oncogene, 24(49), 7301-7309.
http://dx.doi.org/10.1038/sj.onc.1208893
---------- CHICAGO ----------
Ahtiainen, P., Rulli, S.B., Shariatmadari, R., Pelliniemi, L.J., Toppari, J., Poutanen, M., et al. "Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: A study on hCG overexpressing transgenic mice" . Oncogene 24, no. 49 (2005) : 7301-7309.
http://dx.doi.org/10.1038/sj.onc.1208893
---------- MLA ----------
Ahtiainen, P., Rulli, S.B., Shariatmadari, R., Pelliniemi, L.J., Toppari, J., Poutanen, M., et al. "Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: A study on hCG overexpressing transgenic mice" . Oncogene, vol. 24, no. 49, 2005, pp. 7301-7309.
http://dx.doi.org/10.1038/sj.onc.1208893
---------- VANCOUVER ----------
Ahtiainen, P., Rulli, S.B., Shariatmadari, R., Pelliniemi, L.J., Toppari, J., Poutanen, M., et al. Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: A study on hCG overexpressing transgenic mice. Oncogene. 2005;24(49):7301-7309.
http://dx.doi.org/10.1038/sj.onc.1208893