Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels

Autores
Ahtiainen, Pettieri; Sharp, Victoria; Rulli, Susana Beatriz; Rivero Müller, Adolfo; Mamaeva, Veronika; Röytta, Matias; Huhtaniemi, Ilpo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG) beta-subunit. The LH/CG bioactivity is elevated in the mice, with consequent highly stimulated ovarian progesterone (P(4)) production, in the face of normal estrogen secretion. Curiously, despite normal estrogen levels, large prolactinomas developed in these mice, and we provide here several lines of evidence that the elevated P(4) levels are involved in the growth of these estrogen-dependent tumors. The antiprogestin mifepristone inhibited tumor growth, and combined postgonadectomy estradiol/P(4) treatment was more effective than estrogen alone in inducing tumor growth. Evidence for direct growth-promoting effect of P(4) was obtained from cultures of primary mouse pituitary cells and rat somatomammotroph GH3 cells. The mouse tumors and cultured cells revealed stimulation of the cyclin D1/cyclin-dependent kinase 4/retinoblastoma protein/transcription factor E2F1 pathway in the growth response to P(4). If extrapolated to humans, and given the importance of endogenous P(4) and synthetic progestins in female reproductive functions and their pharmacotherapy, it is relevant to revisit the potential role of these hormones in the origin and growth of prolactinomas.
Fil: Ahtiainen, Pettieri. University of Turku; Finlandia
Fil: Sharp, Victoria. Imperial College London; Reino Unido
Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. University of Turku; Finlandia
Fil: Rivero Müller, Adolfo. University of Turku; Finlandia
Fil: Mamaeva, Veronika. University of Turku; Finlandia
Fil: Röytta, Matias. University of Turku; Finlandia
Fil: Huhtaniemi, Ilpo. University of Turku; Finlandia. Imperial College London; Reino Unido
Materia
CHORIONIC GONADOTROPIN
PROLACTINOMA
TRANSGENIC MICE
PITUITARY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14673
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/14673
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levelsAhtiainen, PettieriSharp, VictoriaRulli, Susana BeatrizRivero Müller, AdolfoMamaeva, VeronikaRöytta, MatiasHuhtaniemi, IlpoCHORIONIC GONADOTROPINPROLACTINOMATRANSGENIC MICEPITUITARYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG) beta-subunit. The LH/CG bioactivity is elevated in the mice, with consequent highly stimulated ovarian progesterone (P(4)) production, in the face of normal estrogen secretion. Curiously, despite normal estrogen levels, large prolactinomas developed in these mice, and we provide here several lines of evidence that the elevated P(4) levels are involved in the growth of these estrogen-dependent tumors. The antiprogestin mifepristone inhibited tumor growth, and combined postgonadectomy estradiol/P(4) treatment was more effective than estrogen alone in inducing tumor growth. Evidence for direct growth-promoting effect of P(4) was obtained from cultures of primary mouse pituitary cells and rat somatomammotroph GH3 cells. The mouse tumors and cultured cells revealed stimulation of the cyclin D1/cyclin-dependent kinase 4/retinoblastoma protein/transcription factor E2F1 pathway in the growth response to P(4). If extrapolated to humans, and given the importance of endogenous P(4) and synthetic progestins in female reproductive functions and their pharmacotherapy, it is relevant to revisit the potential role of these hormones in the origin and growth of prolactinomas.Fil: Ahtiainen, Pettieri. University of Turku; FinlandiaFil: Sharp, Victoria. Imperial College London; Reino UnidoFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. University of Turku; FinlandiaFil: Rivero Müller, Adolfo. University of Turku; FinlandiaFil: Mamaeva, Veronika. University of Turku; FinlandiaFil: Röytta, Matias. University of Turku; FinlandiaFil: Huhtaniemi, Ilpo. University of Turku; Finlandia. Imperial College London; Reino UnidoBioscientifica2010-06-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14673Ahtiainen, Pettieri; Sharp, Victoria; Rulli, Susana Beatriz; Rivero Müller, Adolfo; Mamaeva, Veronika; et al.; Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels; Bioscientifica; Endocrine - Related Cancer; 17; 3; 3-6-2010; 611-6211351-00881479-6821enginfo:eu-repo/semantics/altIdentifier/url/http://erc.endocrinology-journals.org/content/17/3/611.longinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881531/info:eu-repo/semantics/altIdentifier/doi/ 10.1677/ERC-10-0016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:17Zoai:ri.conicet.gov.ar:11336/14673instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:17.913CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
title Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
spellingShingle Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
Ahtiainen, Pettieri
CHORIONIC GONADOTROPIN
PROLACTINOMA
TRANSGENIC MICE
PITUITARY
title_short Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_full Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_fullStr Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_full_unstemmed Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_sort Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels
dc.creator.none.fl_str_mv Ahtiainen, Pettieri
Sharp, Victoria
Rulli, Susana Beatriz
Rivero Müller, Adolfo
Mamaeva, Veronika
Röytta, Matias
Huhtaniemi, Ilpo
author Ahtiainen, Pettieri
author_facet Ahtiainen, Pettieri
Sharp, Victoria
Rulli, Susana Beatriz
Rivero Müller, Adolfo
Mamaeva, Veronika
Röytta, Matias
Huhtaniemi, Ilpo
author_role author
author2 Sharp, Victoria
Rulli, Susana Beatriz
Rivero Müller, Adolfo
Mamaeva, Veronika
Röytta, Matias
Huhtaniemi, Ilpo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHORIONIC GONADOTROPIN
PROLACTINOMA
TRANSGENIC MICE
PITUITARY
topic CHORIONIC GONADOTROPIN
PROLACTINOMA
TRANSGENIC MICE
PITUITARY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG) beta-subunit. The LH/CG bioactivity is elevated in the mice, with consequent highly stimulated ovarian progesterone (P(4)) production, in the face of normal estrogen secretion. Curiously, despite normal estrogen levels, large prolactinomas developed in these mice, and we provide here several lines of evidence that the elevated P(4) levels are involved in the growth of these estrogen-dependent tumors. The antiprogestin mifepristone inhibited tumor growth, and combined postgonadectomy estradiol/P(4) treatment was more effective than estrogen alone in inducing tumor growth. Evidence for direct growth-promoting effect of P(4) was obtained from cultures of primary mouse pituitary cells and rat somatomammotroph GH3 cells. The mouse tumors and cultured cells revealed stimulation of the cyclin D1/cyclin-dependent kinase 4/retinoblastoma protein/transcription factor E2F1 pathway in the growth response to P(4). If extrapolated to humans, and given the importance of endogenous P(4) and synthetic progestins in female reproductive functions and their pharmacotherapy, it is relevant to revisit the potential role of these hormones in the origin and growth of prolactinomas.
Fil: Ahtiainen, Pettieri. University of Turku; Finlandia
Fil: Sharp, Victoria. Imperial College London; Reino Unido
Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. University of Turku; Finlandia
Fil: Rivero Müller, Adolfo. University of Turku; Finlandia
Fil: Mamaeva, Veronika. University of Turku; Finlandia
Fil: Röytta, Matias. University of Turku; Finlandia
Fil: Huhtaniemi, Ilpo. University of Turku; Finlandia. Imperial College London; Reino Unido
description The etiology of pituitary adenomas remains largely unknown, with the exception of involvement of estrogens in the formation of prolactinomas. We have examined the molecular pathogenesis of prolactin-producing pituitary adenomas in transgenic female mice expressing the human choriongonadotropin (hCG) beta-subunit. The LH/CG bioactivity is elevated in the mice, with consequent highly stimulated ovarian progesterone (P(4)) production, in the face of normal estrogen secretion. Curiously, despite normal estrogen levels, large prolactinomas developed in these mice, and we provide here several lines of evidence that the elevated P(4) levels are involved in the growth of these estrogen-dependent tumors. The antiprogestin mifepristone inhibited tumor growth, and combined postgonadectomy estradiol/P(4) treatment was more effective than estrogen alone in inducing tumor growth. Evidence for direct growth-promoting effect of P(4) was obtained from cultures of primary mouse pituitary cells and rat somatomammotroph GH3 cells. The mouse tumors and cultured cells revealed stimulation of the cyclin D1/cyclin-dependent kinase 4/retinoblastoma protein/transcription factor E2F1 pathway in the growth response to P(4). If extrapolated to humans, and given the importance of endogenous P(4) and synthetic progestins in female reproductive functions and their pharmacotherapy, it is relevant to revisit the potential role of these hormones in the origin and growth of prolactinomas.
publishDate 2010
dc.date.none.fl_str_mv 2010-06-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/14673
Ahtiainen, Pettieri; Sharp, Victoria; Rulli, Susana Beatriz; Rivero Müller, Adolfo; Mamaeva, Veronika; et al.; Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels; Bioscientifica; Endocrine - Related Cancer; 17; 3; 3-6-2010; 611-621
1351-0088
1479-6821
url http://hdl.handle.net/11336/14673
identifier_str_mv Ahtiainen, Pettieri; Sharp, Victoria; Rulli, Susana Beatriz; Rivero Müller, Adolfo; Mamaeva, Veronika; et al.; Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels; Bioscientifica; Endocrine - Related Cancer; 17; 3; 3-6-2010; 611-621
1351-0088
1479-6821
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://erc.endocrinology-journals.org/content/17/3/611.long
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881531/
info:eu-repo/semantics/altIdentifier/doi/ 10.1677/ERC-10-0016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Bioscientifica
publisher.none.fl_str_mv Bioscientifica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269848467406848
score 13.13397

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