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

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)...

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Autores principales: Ahtiainen, Petteri, Sharp, Victoria, Rulli, Susana B, Rivero-Müller, Adolfo, Mamaeva, Veronika, Röyttä, Matias, Huhtaniemi, Ilpo
Formato: Texto
Lenguaje:English
Publicado: Society for Endocrinology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881531/
https://www.ncbi.nlm.nih.gov/pubmed/20453081
http://dx.doi.org/10.1677/ERC-10-0016
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author Ahtiainen, Petteri
Sharp, Victoria
Rulli, Susana B
Rivero-Müller, Adolfo
Mamaeva, Veronika
Röyttä, Matias
Huhtaniemi, Ilpo
author_facet Ahtiainen, Petteri
Sharp, Victoria
Rulli, Susana B
Rivero-Müller, Adolfo
Mamaeva, Veronika
Röyttä, Matias
Huhtaniemi, Ilpo
author_sort Ahtiainen, Petteri
collection PubMed
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) β-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.
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spelling pubmed-28815312010-09-01 Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels Ahtiainen, Petteri Sharp, Victoria Rulli, Susana B Rivero-Müller, Adolfo Mamaeva, Veronika Röyttä, Matias Huhtaniemi, Ilpo Endocr Relat Cancer Regular Papers 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) β-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. Society for Endocrinology 2010-09 /pmc/articles/PMC2881531/ /pubmed/20453081 http://dx.doi.org/10.1677/ERC-10-0016 Text en © 2010 Society for Endocrinology http://www.endocrinology.org/journals/reuselicence/ This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence (http://www.endocrinology.org/journals/reuselicence/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Papers
Ahtiainen, Petteri
Sharp, Victoria
Rulli, Susana B
Rivero-Müller, Adolfo
Mamaeva, Veronika
Röyttä, Matias
Huhtaniemi, Ilpo
Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
title Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_full Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_fullStr Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_full_unstemmed Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_short Enhanced LH action in transgenic female mice expressing hCGβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
title_sort enhanced lh action in transgenic female mice expressing hcgβ-subunit induces pituitary prolactinomas; the role of high progesterone levels
topic Regular Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881531/
https://www.ncbi.nlm.nih.gov/pubmed/20453081
http://dx.doi.org/10.1677/ERC-10-0016
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