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
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....
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todo:paper_09509232_v24_n49_p7301_Ahtiainen2023-10-03T15:50:30Z 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 Ahtiainen, P. Rulli, S.B. Shariatmadari, R. Pelliniemi, L.J. Toppari, J. Poutanen, M. Huhtaniemi, I.T. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09509232_v24_n49_p7301_Ahtiainen |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Ahtiainen, P. Rulli, S.B. Shariatmadari, R. Pelliniemi, L.J. Toppari, J. Poutanen, M. Huhtaniemi, I.T. 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Ahtiainen, P. Rulli, S.B. Shariatmadari, R. Pelliniemi, L.J. Toppari, J. Poutanen, M. Huhtaniemi, I.T. |
| author_facet |
Ahtiainen, P. Rulli, S.B. Shariatmadari, R. Pelliniemi, L.J. Toppari, J. Poutanen, M. Huhtaniemi, I.T. |
| author_sort |
Ahtiainen, P. |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| url |
http://hdl.handle.net/20.500.12110/paper_09509232_v24_n49_p7301_Ahtiainen |
| work_keys_str_mv |
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