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Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling
Casein kinase 1α (CK1α) is present in multiple cellular organelles and plays various roles in regulating neuroendocrine metabolism. Herein, we investigated the underlying function and mechanisms of CK1α-regulated thyrotropin (thyroid-stimulating hormone (TSH)) synthesis in a murine model. Immunohist...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138882/ https://www.ncbi.nlm.nih.gov/pubmed/37108197 http://dx.doi.org/10.3390/ijms24087034 |
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author | Wang, Bingjie Zhang, Jinglin Zhang, Di Lu, Chenyang Liu, Hui Gao, Qiao Niu, Tongjuan Yin, Mengqing Cui, Sheng |
author_facet | Wang, Bingjie Zhang, Jinglin Zhang, Di Lu, Chenyang Liu, Hui Gao, Qiao Niu, Tongjuan Yin, Mengqing Cui, Sheng |
author_sort | Wang, Bingjie |
collection | PubMed |
description | Casein kinase 1α (CK1α) is present in multiple cellular organelles and plays various roles in regulating neuroendocrine metabolism. Herein, we investigated the underlying function and mechanisms of CK1α-regulated thyrotropin (thyroid-stimulating hormone (TSH)) synthesis in a murine model. Immunohistochemistry and immunofluorescence staining were performed to detect CK1α expression in murine pituitary tissue and its localization to specific cell types. Tshb mRNA expression in anterior pituitary was detected using real-time and radioimmunoassay techniques after CK1α activity was promoted and inhibited in vivo and in vitro. Relationships among TRH/L-T4, CK1α, and TSH were analyzed with TRH and L-T4 treatment, as well as thyroidectomy, in vivo. In mice, CK1α was expressed at higher levels in the pituitary gland tissue than in the thyroid, adrenal gland, or liver. However, inhibiting endogenous CK1α activity in the anterior pituitary and primary pituitary cells significantly increased TSH expression and attenuated the inhibitory effect of L-T4 on TSH. In contrast, CK1α activation weakened TSH stimulation by thyrotropin-releasing hormone (TRH) by suppressing protein kinase C (PKC)/extracellular signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling. CK1α, as a negative regulator, mediates TRH and L-T4 upstream signaling by targeting PKC, thus affecting TSH expression and downregulating ERK1/2 phosphorylation and CREB transcriptional activity. |
format | Online Article Text |
id | pubmed-10138882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101388822023-04-28 Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling Wang, Bingjie Zhang, Jinglin Zhang, Di Lu, Chenyang Liu, Hui Gao, Qiao Niu, Tongjuan Yin, Mengqing Cui, Sheng Int J Mol Sci Article Casein kinase 1α (CK1α) is present in multiple cellular organelles and plays various roles in regulating neuroendocrine metabolism. Herein, we investigated the underlying function and mechanisms of CK1α-regulated thyrotropin (thyroid-stimulating hormone (TSH)) synthesis in a murine model. Immunohistochemistry and immunofluorescence staining were performed to detect CK1α expression in murine pituitary tissue and its localization to specific cell types. Tshb mRNA expression in anterior pituitary was detected using real-time and radioimmunoassay techniques after CK1α activity was promoted and inhibited in vivo and in vitro. Relationships among TRH/L-T4, CK1α, and TSH were analyzed with TRH and L-T4 treatment, as well as thyroidectomy, in vivo. In mice, CK1α was expressed at higher levels in the pituitary gland tissue than in the thyroid, adrenal gland, or liver. However, inhibiting endogenous CK1α activity in the anterior pituitary and primary pituitary cells significantly increased TSH expression and attenuated the inhibitory effect of L-T4 on TSH. In contrast, CK1α activation weakened TSH stimulation by thyrotropin-releasing hormone (TRH) by suppressing protein kinase C (PKC)/extracellular signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling. CK1α, as a negative regulator, mediates TRH and L-T4 upstream signaling by targeting PKC, thus affecting TSH expression and downregulating ERK1/2 phosphorylation and CREB transcriptional activity. MDPI 2023-04-11 /pmc/articles/PMC10138882/ /pubmed/37108197 http://dx.doi.org/10.3390/ijms24087034 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Bingjie Zhang, Jinglin Zhang, Di Lu, Chenyang Liu, Hui Gao, Qiao Niu, Tongjuan Yin, Mengqing Cui, Sheng Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling |
title | Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling |
title_full | Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling |
title_fullStr | Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling |
title_full_unstemmed | Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling |
title_short | Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling |
title_sort | casein kinase 1α as a novel factor affects thyrotropin synthesis via pkc/erk/creb signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138882/ https://www.ncbi.nlm.nih.gov/pubmed/37108197 http://dx.doi.org/10.3390/ijms24087034 |
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