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

Andrea Balogh, Eva Karpati, Andrea E. Schneider, Szabolcs Hetey, Andras Szilagyi, Kata Juhasz, Gloria Laszlo, P. Hupuczi, P. Závodszky, Zoltan Papp, J. Matkó, Nandor Gabor Than

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number4
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Sex Hormone-Binding Globulin
Estradiol
Lymphocytes
Membranes
B-Lymphocytes
Estrogen Receptors
T-Lymphocytes
Estrogen Receptor alpha
Lymphoid Tissue
Computer Simulation
Pregnant Women
Phosphorylation
Cell Membrane
Lipids
Cell Line

ASJC Scopus subject areas

  • General

Cite this

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, P.; Závodszky, P.; Papp, Zoltan; Matkó, J.; Than, Nandor Gabor.

In: Scientific Reports, Vol. 9, No. 1, 4, 01.12.2019.

Research output: Contribution to journalArticle

Balogh, Andrea ; Karpati, Eva ; Schneider, Andrea E. ; Hetey, Szabolcs ; Szilagyi, Andras ; Juhasz, Kata ; Laszlo, Gloria ; Hupuczi, P. ; Závodszky, P. ; Papp, Zoltan ; Matkó, J. ; Than, Nandor Gabor. / Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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