Cargando…

Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor

The complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover...

Descripción completa

Detalles Bibliográficos
Autores principales: Balogh, Andrea, Karpati, Eva, Schneider, Andrea E., Hetey, Szabolcs, Szilagyi, Andras, Juhasz, Kata, Laszlo, Gloria, Hupuczi, Petronella, Zavodszky, Peter, Papp, Zoltan, Matko, Janos, Than, Nandor Gabor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327036/
https://www.ncbi.nlm.nih.gov/pubmed/30626909
http://dx.doi.org/10.1038/s41598-018-36882-3
_version_ 1783386396346548224
author Balogh, Andrea
Karpati, Eva
Schneider, Andrea E.
Hetey, Szabolcs
Szilagyi, Andras
Juhasz, Kata
Laszlo, Gloria
Hupuczi, Petronella
Zavodszky, Peter
Papp, Zoltan
Matko, Janos
Than, Nandor Gabor
author_facet Balogh, Andrea
Karpati, Eva
Schneider, Andrea E.
Hetey, Szabolcs
Szilagyi, Andras
Juhasz, Kata
Laszlo, Gloria
Hupuczi, Petronella
Zavodszky, Peter
Papp, Zoltan
Matko, Janos
Than, Nandor Gabor
author_sort Balogh, Andrea
collection PubMed
description The complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover, the expression of SHBG and its internalization by potential receptors, as well as the influence of SHBG on estradiol uptake and signaling in lymphocytes has remained unexplored. Here, we found that human and mouse T cells expressed SHBG intrinsically. In addition, B lymphoid cell lines as well as both primary B and T lymphocytes bound and internalized external SHBG, and the amount of plasma membrane-bound SHBG decreased in B cells of pregnant compared to non-pregnant women. As potential mediators of this process, SHBG receptor candidates expressed by lymphocytes were identified in silico, including estrogen receptor (ER) alpha. Furthermore, cell surface-bound SHBG was detected in close proximity to membrane ERs while highly colocalizing with lipid rafts. The SHBG-membrane ER interaction was found functional since SHBG promoted estradiol uptake by lymphocytes and subsequently influenced Erk1/2 phosphorylation. In conclusion, the SHBG-SHBG receptor-membrane ER complex participates in the rapid estradiol signaling in lymphocytes, and this pathway may be altered in B cells in pregnant women.
format Online
Article
Text
id pubmed-6327036
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63270362019-01-11 Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor Balogh, Andrea Karpati, Eva Schneider, Andrea E. Hetey, Szabolcs Szilagyi, Andras Juhasz, Kata Laszlo, Gloria Hupuczi, Petronella Zavodszky, Peter Papp, Zoltan Matko, Janos Than, Nandor Gabor Sci Rep Article The complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover, the expression of SHBG and its internalization by potential receptors, as well as the influence of SHBG on estradiol uptake and signaling in lymphocytes has remained unexplored. Here, we found that human and mouse T cells expressed SHBG intrinsically. In addition, B lymphoid cell lines as well as both primary B and T lymphocytes bound and internalized external SHBG, and the amount of plasma membrane-bound SHBG decreased in B cells of pregnant compared to non-pregnant women. As potential mediators of this process, SHBG receptor candidates expressed by lymphocytes were identified in silico, including estrogen receptor (ER) alpha. Furthermore, cell surface-bound SHBG was detected in close proximity to membrane ERs while highly colocalizing with lipid rafts. The SHBG-membrane ER interaction was found functional since SHBG promoted estradiol uptake by lymphocytes and subsequently influenced Erk1/2 phosphorylation. In conclusion, the SHBG-SHBG receptor-membrane ER complex participates in the rapid estradiol signaling in lymphocytes, and this pathway may be altered in B cells in pregnant women. Nature Publishing Group UK 2019-01-09 /pmc/articles/PMC6327036/ /pubmed/30626909 http://dx.doi.org/10.1038/s41598-018-36882-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Balogh, Andrea
Karpati, Eva
Schneider, Andrea E.
Hetey, Szabolcs
Szilagyi, Andras
Juhasz, Kata
Laszlo, Gloria
Hupuczi, Petronella
Zavodszky, Peter
Papp, Zoltan
Matko, Janos
Than, Nandor Gabor
Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
title Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
title_full Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
title_fullStr Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
title_full_unstemmed Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
title_short Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
title_sort sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327036/
https://www.ncbi.nlm.nih.gov/pubmed/30626909
http://dx.doi.org/10.1038/s41598-018-36882-3
work_keys_str_mv AT baloghandrea sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT karpatieva sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT schneiderandreae sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT heteyszabolcs sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT szilagyiandras sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT juhaszkata sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT laszlogloria sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT hupuczipetronella sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT zavodszkypeter sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT pappzoltan sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT matkojanos sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor
AT thannandorgabor sexhormonebindingglobulinprovidesanovelentrypathwayforestradiolandinfluencessubsequentsignalinginlymphocytesviamembranereceptor