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 |
Referencias:
- Ariyaratne, H.B., Mendis-Handagama, C.S., (2000) Biol. Reprod., 62, pp. 680-690
- Cattanach, B.M., Iddon, C.A., Charlton, H.M., Chiappa, S.A., Fink, G., (1977) Nature, 269, pp. 338-340
- Chemes, H.E., (1996) The Leydig Cell, pp. 175-202. , Payne AH, Hardy MP and Russell LD (eds). Cache River Press: Vienna
- Christensen, A.K., Peacock, K.C., (1980) Biol. Reprod., 22, pp. 383-391
- Clegg, E.D., Cook, J.C., Chapin, R.E., Foster, P.M., Daston, G.P., (1997) Reprod. Toxicol., 11, pp. 107-121
- Cook, J.C., Klinefelter, G.R., Hardisty, J.F., Sharpe, R.M., Foster, P.M., (1999) Crit. Rev. Toxicol., 29, pp. 169-261
- Habert, R., Lejeune, H., Saez, J.M., (2001) Mol. Cell. Endocrinol., 179, pp. 47-74
- Hardy, M.P., Zirkin, B.R., Ewing, L.L., (1989) Endocrinology, 124, pp. 762-770
- Hirakawa, T., Galet, C., Ascoli, M., (2002) Endocrinology, 143, pp. 1026-1035
- Huhtaniemi, I., Nikula, H., Rannikko, S., (1985) J. Clin. Endocrinol. Metab., 61, pp. 698-704
- Huhtaniemi, I.T., Nozu, K., Warren, D.W., Dufau, M.L., Catt, K.J., (1982) Endocrinology, 111, pp. 1711-1720
- Huhtaniemi, I.T., Warren, D.W., Catt, K.J., (1985) Biol. Reprod., 32, pp. 721-732
- Huseby, R.A., (1980) Cancer Res., 40, pp. 1006-1013
- Kananen, K., Rilianawati, Paukku, T., Markkula, M., Rainio, E.M., Huhtanemi, I., (1997) Endocrinology, 138, pp. 3521-3531
- Kendall, S.K., Samuelson, L.C., Saunders, T.L., Wood, R.I., Camper, S.A., (1995) Genes Dev., 9, pp. 2007-2019
- Keri, R.A., Lozada, K.L., Abdul-Karim, F.W., Nadeau, J.H., Nilson, J.H., (2000) Proc. Natl. Acad. Sci. USA, 97, pp. 383-387
- Kerr, J.B., Knell, C.M., (1988) Development, 103, pp. 535-544
- Korenbrot, C.C., Huhtaniemi, I.T., Weiner, R.I., (1977) Biol. Reprod., 17, pp. 298-303
- Kumar, T.R., Wang, Y., Matzuk, M.M., (1996) Endocrinology, 137, pp. 4210-4216
- Kuopio, T., Pelliniemi, L.J., Huhtaniemi, I., (1989) Biol. Reprod., 40, pp. 135-143
- Li, X., Nokkala, E., Yan, W., Streng, T., Saarinen, N., Warri, A., Huhtaniemi, I., Poutanen, M., (2001) Endocrinology, 142, pp. 2435-2442
- Liu, G., Duranteau, L., Carel, J.C., Monroe, J., Doyle, D.A., Shenker, A., (1999) N. Engl. J. Med., 341, pp. 1731-1736
- Ma, X., Dong, Y., Matzuk, M.M., Kumar, T.R., (2004) Proc. Natl. Acad. Sci. USA, 101, pp. 17294-17299
- Matzuk, M.M., DeMayo, F.J., Hadsell, L.A., Kumar, T.R., (2003) Biol. Reprod., 69, pp. 338-346
- Mikola, M., Kero, J., Nilson, J.H., Keri, R.A., Poutanen, M., Huhtaniemi, I., (2003) Oncogene, 22, pp. 3269-3278
- Navickis, R.J., Shimkin, M.B., Hsueh, A.J., (1981) Cancer Res., 41, pp. 1646-1651
- O'Shaughnessy, P.J., Baker, P., Sohnius, U., Haavisto, A.M., Charlton, H.M., Huhtaniemi, I., (1998) Endocrinology, 139, pp. 1141-1146
- O'Shaughnessy, P.J., Johnston, H., Willerton, L., Baker, P.J., (2002) J. Cell. Sci., 115, pp. 3491-3496
- O'Shaughnessy, P.J., Willerton, L., Baker, P.J., (2002) Biol. Reprod., 66, pp. 966-975
- Pakarinen, P., Vihko, K.K., Voutilainen, R., Huhtaniemi, I., (1990) Endocrinology, 127, pp. 2469-2474
- Parrott, J.A., Doraiswamy, V., Kim, G., Mosher, R., Skinner, M.K., (2001) Mol. Cell. Endocrinol., 172, pp. 213-222
- Prahalada, S., Majka, J.A., Soper, K.A., Nett, T.M., Bagdon, W.J., Peter, C.P., Burek, J.D., Van Zwieten, M.J., (1994) Fundam. Appl. Toxicol., 22, pp. 211-219
- Richter-Unruh, A., Wessels, H.T., Menken, U., Bergmann, M., Schmittmann-Ohters, K., Schaper, J., Tappeser, S., Hauffa, B.P., (2002) J. Clin. Endocrinol. Metab., 87, pp. 1052-1056
- Rulli, S.B., Ahtiainen, P., Makela, S., Toppari, J., Poutanen, M., Huhtaniemi, I., (2003) Endocrinology, 144, pp. 4980-4990
- Rulli, S.B., Kuorelahti, A., Karaer, O., Pelliniemi, L.J., Poutanen, M., Huhtaniemi, I., (2002) Endocrinology, 143, pp. 4084-4095
- Simon, W.E., Albrecht, M., Hansel, M., Dietel, M., Holzel, F., (1983) J. Natl. Cancer Inst., 70, pp. 839-845
- Sundstrom, J., Pelliniemi, L.J., Kuopio, T., Verajankorva, E., Frojdman, K., Harley, V., Salminen, E., Pollanen, P., (1999) Br. J. Cancer, 80, pp. 149-160
- Themmen, A.P.N., Huhtaniemi, I.T., (2000) Endocr. Rev., 21, pp. 551-583
- Wise, P.M., Krajnak, K.M., Kashon, M.L., (1996) Science, 273, pp. 67-70
- Zhang, F.P., Hamalainen, T., Kaipia, A., Pakarinen, P., Huhtaniemi, I., (1994) Endocrinology, 134, pp. 2206-2213
- Zhang, F.P., Poutanen, M., Wilbertz, J., Huhtaniemi, I., (2001) Mol. Endocrinol., 15, pp. 172-183
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