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Phosphodiesterases and cAMP Pathway in Pituitary Diseases

Human phosphodiesterases (PDEs) comprise a complex superfamily of enzymes derived from 24 genes separated into 11 PDE gene families (PDEs 1–11), expressed in different tissues and cells, including heart and brain. The isoforms PDE4, PDE7, and PDE8 are specific for the second messenger cAMP, which is...

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Autores principales: Bizzi, Mariana Ferreira, Bolger, Graeme B., Korbonits, Márta, Ribeiro-Oliveira Jr., Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433792/
https://www.ncbi.nlm.nih.gov/pubmed/30941100
http://dx.doi.org/10.3389/fendo.2019.00141
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author Bizzi, Mariana Ferreira
Bolger, Graeme B.
Korbonits, Márta
Ribeiro-Oliveira Jr., Antonio
author_facet Bizzi, Mariana Ferreira
Bolger, Graeme B.
Korbonits, Márta
Ribeiro-Oliveira Jr., Antonio
author_sort Bizzi, Mariana Ferreira
collection PubMed
description Human phosphodiesterases (PDEs) comprise a complex superfamily of enzymes derived from 24 genes separated into 11 PDE gene families (PDEs 1–11), expressed in different tissues and cells, including heart and brain. The isoforms PDE4, PDE7, and PDE8 are specific for the second messenger cAMP, which is responsible for mediating diverse physiological actions involving different hormones and neurotransmitters. The cAMP pathway plays an important role in the development and function of endocrine tissues while phosphodiesterases are responsible for ensuring the appropriate intensity of the actions of this pathway by hydrolyzing cAMP to its inactive form 5'-AMP. PDE1, PDE2, PDE4, and PDE11A are highly expressed in the pituitary, and overexpression of some PDE4 isoforms have been demonstrated in different pituitary adenoma subtypes. This observed over-expression in pituitary adenomas, although of unknown etiology, has been considered a compensatory response to tumorigenesis. PDE4A4/5 has a unique interaction with the co-chaperone aryl hydrocarbon receptor-interacting protein (AIP), a protein implicated in somatotroph tumorigenesis via germline loss-of-function mutations. Based on the association of low PDE4A4 expression with germline AIP-mutation-positive samples, the available data suggest that lack of AIP hinders the upregulation of PDE4A4 protein seen in sporadic somatotrophinomas. This unique disturbance of the cAMP-PDE pathway observed in the majority of AIP-mutation positive adenomas could contribute to their well-described poor response to somatostatin analogs and may support a role in tumorigenesis.
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spelling pubmed-64337922019-04-02 Phosphodiesterases and cAMP Pathway in Pituitary Diseases Bizzi, Mariana Ferreira Bolger, Graeme B. Korbonits, Márta Ribeiro-Oliveira Jr., Antonio Front Endocrinol (Lausanne) Endocrinology Human phosphodiesterases (PDEs) comprise a complex superfamily of enzymes derived from 24 genes separated into 11 PDE gene families (PDEs 1–11), expressed in different tissues and cells, including heart and brain. The isoforms PDE4, PDE7, and PDE8 are specific for the second messenger cAMP, which is responsible for mediating diverse physiological actions involving different hormones and neurotransmitters. The cAMP pathway plays an important role in the development and function of endocrine tissues while phosphodiesterases are responsible for ensuring the appropriate intensity of the actions of this pathway by hydrolyzing cAMP to its inactive form 5'-AMP. PDE1, PDE2, PDE4, and PDE11A are highly expressed in the pituitary, and overexpression of some PDE4 isoforms have been demonstrated in different pituitary adenoma subtypes. This observed over-expression in pituitary adenomas, although of unknown etiology, has been considered a compensatory response to tumorigenesis. PDE4A4/5 has a unique interaction with the co-chaperone aryl hydrocarbon receptor-interacting protein (AIP), a protein implicated in somatotroph tumorigenesis via germline loss-of-function mutations. Based on the association of low PDE4A4 expression with germline AIP-mutation-positive samples, the available data suggest that lack of AIP hinders the upregulation of PDE4A4 protein seen in sporadic somatotrophinomas. This unique disturbance of the cAMP-PDE pathway observed in the majority of AIP-mutation positive adenomas could contribute to their well-described poor response to somatostatin analogs and may support a role in tumorigenesis. Frontiers Media S.A. 2019-03-19 /pmc/articles/PMC6433792/ /pubmed/30941100 http://dx.doi.org/10.3389/fendo.2019.00141 Text en Copyright © 2019 Bizzi, Bolger, Korbonits and Ribeiro-Oliveira. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Bizzi, Mariana Ferreira
Bolger, Graeme B.
Korbonits, Márta
Ribeiro-Oliveira Jr., Antonio
Phosphodiesterases and cAMP Pathway in Pituitary Diseases
title Phosphodiesterases and cAMP Pathway in Pituitary Diseases
title_full Phosphodiesterases and cAMP Pathway in Pituitary Diseases
title_fullStr Phosphodiesterases and cAMP Pathway in Pituitary Diseases
title_full_unstemmed Phosphodiesterases and cAMP Pathway in Pituitary Diseases
title_short Phosphodiesterases and cAMP Pathway in Pituitary Diseases
title_sort phosphodiesterases and camp pathway in pituitary diseases
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433792/
https://www.ncbi.nlm.nih.gov/pubmed/30941100
http://dx.doi.org/10.3389/fendo.2019.00141
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