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SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues

Disclosure: J. Lim: None. In mammals, the control of cell fate is imperative to the development of multicellular organisms as well as tissue homeostasis/regeneration in the adult. The anterior pituitary (AP) controls growth, metabolism, reproduction, and stress responses through the synthesis and se...

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Autor principal: Lim, Juchan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10553884/
http://dx.doi.org/10.1210/jendso/bvad114.1332
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author Lim, Juchan
author_facet Lim, Juchan
author_sort Lim, Juchan
collection PubMed
description Disclosure: J. Lim: None. In mammals, the control of cell fate is imperative to the development of multicellular organisms as well as tissue homeostasis/regeneration in the adult. The anterior pituitary (AP) controls growth, metabolism, reproduction, and stress responses through the synthesis and secretion of specific hormones by distinct AP cell lineages. Interestingly, the anterior pituitary exhibits a high level of adult cell plasticity that allows committed hormone-producing cells to alter their cell fate and produce different hormones to meet altered organismal demands. The molecular mechanisms underlying this adult cell plasticity have not been fully characterized. To investigate the mechanism(s) of pituitary cell transdifferentiation, our lab has employed a rat GH3 cell culture model that undergoes somatotrope to lactotrope conversion in response to a cocktail of 3 growth factors (EGF, estradiol and insulin). Upon stimulation of lactotrope transdifferentiation, we confirmed a significant reduction of Growth hormone (Gh1) and reciprocal elevation of Prolactin (Prl) protein and transcript levels in the treated group compared to untreated controls. Proteomic and transcriptomic analyses from the same samples detected upregulation of 124 proteins and 553 transcripts and downregulation of 28 proteins and 556 transcripts respectively. Gene ontology analyses identified a number of upregulated proteins involved in autophagy (e.g. autolysosome), MTORC1 signaling, and a number of upregulated transcripts involved in the regulation of cell proliferation and apoptosis. A number of the upregulated proteins and transcripts are involved in Epithelial-to-mesenchymal transition (EMT) and metabolic change (i.e. glycolysis, hypoxia), while downregulated transcripts involved in neurogenesis (i.e. Notch1, Notch2, Sox2, Sox5). Further, differential expression analyses comparing the proteomic and transcriptomic levels of the treated vs. control GH3 cells identified a number of upregulated proteins with no change in their corresponding transcripts related to MTORC1 signaling and glycolysis as well as a number of unchanged proteins with corresponding upregulated transcripts involved in mitochondrial activity suggesting a broad role for post-transcriptional regulation during transdifferentiation. In a complementary in vivo study, we assessed pituitary cell fate changes in response to hypothyroidism, using a similar integrated proteogenomic profiling. Together, we identify a number of altered molecular pathways that underlie distinct pituitary cell plasticity responses to physiological cues. Presentation: Saturday, June 17, 2023
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spelling pubmed-105538842023-10-06 SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues Lim, Juchan J Endocr Soc Neuroendocrinology And Pituitary Disclosure: J. Lim: None. In mammals, the control of cell fate is imperative to the development of multicellular organisms as well as tissue homeostasis/regeneration in the adult. The anterior pituitary (AP) controls growth, metabolism, reproduction, and stress responses through the synthesis and secretion of specific hormones by distinct AP cell lineages. Interestingly, the anterior pituitary exhibits a high level of adult cell plasticity that allows committed hormone-producing cells to alter their cell fate and produce different hormones to meet altered organismal demands. The molecular mechanisms underlying this adult cell plasticity have not been fully characterized. To investigate the mechanism(s) of pituitary cell transdifferentiation, our lab has employed a rat GH3 cell culture model that undergoes somatotrope to lactotrope conversion in response to a cocktail of 3 growth factors (EGF, estradiol and insulin). Upon stimulation of lactotrope transdifferentiation, we confirmed a significant reduction of Growth hormone (Gh1) and reciprocal elevation of Prolactin (Prl) protein and transcript levels in the treated group compared to untreated controls. Proteomic and transcriptomic analyses from the same samples detected upregulation of 124 proteins and 553 transcripts and downregulation of 28 proteins and 556 transcripts respectively. Gene ontology analyses identified a number of upregulated proteins involved in autophagy (e.g. autolysosome), MTORC1 signaling, and a number of upregulated transcripts involved in the regulation of cell proliferation and apoptosis. A number of the upregulated proteins and transcripts are involved in Epithelial-to-mesenchymal transition (EMT) and metabolic change (i.e. glycolysis, hypoxia), while downregulated transcripts involved in neurogenesis (i.e. Notch1, Notch2, Sox2, Sox5). Further, differential expression analyses comparing the proteomic and transcriptomic levels of the treated vs. control GH3 cells identified a number of upregulated proteins with no change in their corresponding transcripts related to MTORC1 signaling and glycolysis as well as a number of unchanged proteins with corresponding upregulated transcripts involved in mitochondrial activity suggesting a broad role for post-transcriptional regulation during transdifferentiation. In a complementary in vivo study, we assessed pituitary cell fate changes in response to hypothyroidism, using a similar integrated proteogenomic profiling. Together, we identify a number of altered molecular pathways that underlie distinct pituitary cell plasticity responses to physiological cues. Presentation: Saturday, June 17, 2023 Oxford University Press 2023-10-05 /pmc/articles/PMC10553884/ http://dx.doi.org/10.1210/jendso/bvad114.1332 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Neuroendocrinology And Pituitary
Lim, Juchan
SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
title SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
title_full SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
title_fullStr SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
title_full_unstemmed SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
title_short SAT599 Molecular Analysis Of Pituitary Transdifferentiation In Response To Physiological Cues
title_sort sat599 molecular analysis of pituitary transdifferentiation in response to physiological cues
topic Neuroendocrinology And Pituitary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10553884/
http://dx.doi.org/10.1210/jendso/bvad114.1332
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