Multiple sites of tumorigenesis in transgenic mice overproducing hCG
We have produced transgenic (TG) mice expressing under the ubiquitin C promoter either the glycoprotein hormone common α-subunit (Cα) or human chorionic gonadotropin (hCG) β-subunit. Cα overexpression alone had no phenotypic effect, but the hCGβ expressing females, presenting with moderately elevate...
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2005
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v234_n1-2_p117_Huhtaniemi http://hdl.handle.net/20.500.12110/paper_03037207_v234_n1-2_p117_Huhtaniemi |
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paper:paper_03037207_v234_n1-2_p117_Huhtaniemi2023-06-08T15:29:04Z Multiple sites of tumorigenesis in transgenic mice overproducing hCG Choriongonadotropin Leydig cell adenoma Luteoma Mammary tumours Ovarian tumours Pituitary tumours Prolactinoma Teratoma Transgenic mice chorionic gonadotropin luteinizing hormone prolactin protein subunit sex hormone ubiquitin C adulthood alpha chain blood level breast carcinoma breast tumor cancer localization carcinogenesis cell type conference paper gene overexpression germ cell tumor gonadectomy hormone release human hyperplasia hypophysis hypophysis tumor Leydig cell luteinization luteoma mammary gland nonhuman ovary teratoma ovary tumor pathophysiology perinatal period phenotype priority journal prolactinoma protein expression seminiferous tubule epithelium somatic cell transgene transgenic mouse We have produced transgenic (TG) mice expressing under the ubiquitin C promoter either the glycoprotein hormone common α-subunit (Cα) or human chorionic gonadotropin (hCG) β-subunit. Cα overexpression alone had no phenotypic effect, but the hCGβ expressing females, presenting with moderately elevated levels of bioactive LH/hCG, due to dimerization of the TG hCGβ with endogenous Cα, developed multiple gonadal and extragonadal neoplasias. Crosses of the Cα and hCGβ mice (hCGαβ) had >1000-fold elevated hCG levels, due to ubiquitous transgene expression, and presented with more aggressive tumour formation. The ovaries displayed initially strong luteinisation of all somatic cell types, leading to formation of luteomas, and subsequently to germ cell tumours (teratomas). The pituitary glands of TG females were massively enlarged, up to >100 mg, developing macroprolactinomas with very high prolactin (PRL) production. This endocrine response probably induced breast cancers in the mice. In contrast to the females, similar high levels of hCG in male mice had only marginal effects in adulthood, with slight Leydig cell hyperplasia and atrophy in the seminiferous epithelium. However, clear Leydig cell adenomas were observed in postnatal mice, apparently originating from fetal Leydig cells. In conclusion, these studies demonstrate marked tumorigenic effects of supraphysiological hCG levels in female mice, but clear resistance to similar changes in males. The extragonadal tumours were induced by hCG stimulated aberrant ovarian endocrine function, rather than by direct hCG action, because gonadectomy prevented all extragonadal phenotypes despite persistent hCG elevation. The phenotypes of the TG mice apparently represent exaggerated responses to hCG/LH and/or gonadal steroids. It remains to be explored to what extent they simulate respective responses in humans to pathophysiological elevation of the same hormones. © 2005 Elsevier Ireland Ltd. All rights reserved. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v234_n1-2_p117_Huhtaniemi http://hdl.handle.net/20.500.12110/paper_03037207_v234_n1-2_p117_Huhtaniemi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Choriongonadotropin Leydig cell adenoma Luteoma Mammary tumours Ovarian tumours Pituitary tumours Prolactinoma Teratoma Transgenic mice chorionic gonadotropin luteinizing hormone prolactin protein subunit sex hormone ubiquitin C adulthood alpha chain blood level breast carcinoma breast tumor cancer localization carcinogenesis cell type conference paper gene overexpression germ cell tumor gonadectomy hormone release human hyperplasia hypophysis hypophysis tumor Leydig cell luteinization luteoma mammary gland nonhuman ovary teratoma ovary tumor pathophysiology perinatal period phenotype priority journal prolactinoma protein expression seminiferous tubule epithelium somatic cell transgene transgenic mouse |
| spellingShingle |
Choriongonadotropin Leydig cell adenoma Luteoma Mammary tumours Ovarian tumours Pituitary tumours Prolactinoma Teratoma Transgenic mice chorionic gonadotropin luteinizing hormone prolactin protein subunit sex hormone ubiquitin C adulthood alpha chain blood level breast carcinoma breast tumor cancer localization carcinogenesis cell type conference paper gene overexpression germ cell tumor gonadectomy hormone release human hyperplasia hypophysis hypophysis tumor Leydig cell luteinization luteoma mammary gland nonhuman ovary teratoma ovary tumor pathophysiology perinatal period phenotype priority journal prolactinoma protein expression seminiferous tubule epithelium somatic cell transgene transgenic mouse Multiple sites of tumorigenesis in transgenic mice overproducing hCG |
| topic_facet |
Choriongonadotropin Leydig cell adenoma Luteoma Mammary tumours Ovarian tumours Pituitary tumours Prolactinoma Teratoma Transgenic mice chorionic gonadotropin luteinizing hormone prolactin protein subunit sex hormone ubiquitin C adulthood alpha chain blood level breast carcinoma breast tumor cancer localization carcinogenesis cell type conference paper gene overexpression germ cell tumor gonadectomy hormone release human hyperplasia hypophysis hypophysis tumor Leydig cell luteinization luteoma mammary gland nonhuman ovary teratoma ovary tumor pathophysiology perinatal period phenotype priority journal prolactinoma protein expression seminiferous tubule epithelium somatic cell transgene transgenic mouse |
| description |
We have produced transgenic (TG) mice expressing under the ubiquitin C promoter either the glycoprotein hormone common α-subunit (Cα) or human chorionic gonadotropin (hCG) β-subunit. Cα overexpression alone had no phenotypic effect, but the hCGβ expressing females, presenting with moderately elevated levels of bioactive LH/hCG, due to dimerization of the TG hCGβ with endogenous Cα, developed multiple gonadal and extragonadal neoplasias. Crosses of the Cα and hCGβ mice (hCGαβ) had >1000-fold elevated hCG levels, due to ubiquitous transgene expression, and presented with more aggressive tumour formation. The ovaries displayed initially strong luteinisation of all somatic cell types, leading to formation of luteomas, and subsequently to germ cell tumours (teratomas). The pituitary glands of TG females were massively enlarged, up to >100 mg, developing macroprolactinomas with very high prolactin (PRL) production. This endocrine response probably induced breast cancers in the mice. In contrast to the females, similar high levels of hCG in male mice had only marginal effects in adulthood, with slight Leydig cell hyperplasia and atrophy in the seminiferous epithelium. However, clear Leydig cell adenomas were observed in postnatal mice, apparently originating from fetal Leydig cells. In conclusion, these studies demonstrate marked tumorigenic effects of supraphysiological hCG levels in female mice, but clear resistance to similar changes in males. The extragonadal tumours were induced by hCG stimulated aberrant ovarian endocrine function, rather than by direct hCG action, because gonadectomy prevented all extragonadal phenotypes despite persistent hCG elevation. The phenotypes of the TG mice apparently represent exaggerated responses to hCG/LH and/or gonadal steroids. It remains to be explored to what extent they simulate respective responses in humans to pathophysiological elevation of the same hormones. © 2005 Elsevier Ireland Ltd. All rights reserved. |
| title |
Multiple sites of tumorigenesis in transgenic mice overproducing hCG |
| title_short |
Multiple sites of tumorigenesis in transgenic mice overproducing hCG |
| title_full |
Multiple sites of tumorigenesis in transgenic mice overproducing hCG |
| title_fullStr |
Multiple sites of tumorigenesis in transgenic mice overproducing hCG |
| title_full_unstemmed |
Multiple sites of tumorigenesis in transgenic mice overproducing hCG |
| title_sort |
multiple sites of tumorigenesis in transgenic mice overproducing hcg |
| publishDate |
2005 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v234_n1-2_p117_Huhtaniemi http://hdl.handle.net/20.500.12110/paper_03037207_v234_n1-2_p117_Huhtaniemi |
| _version_ |
1768543368441233408 |