Steroid hormone bioavailability is controlled by the lymphatic system

Abstract The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cel...

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Autores principales:	Rahel Klossner, Michael Groessl, Nadine Schumacher, Michaela Fux, Geneviève Escher, Sophia Verouti, Heidi Jamin, Bruno Vogt, Markus G. Mohaupt, Carine Gennari-Moser
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75cad88b199f45d5bab5f61446be107f
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spelling	oai:doaj.org-article:75cad88b199f45d5bab5f61446be107f2021-12-02T14:41:56ZSteroid hormone bioavailability is controlled by the lymphatic system10.1038/s41598-021-88508-w2045-2322https://doaj.org/article/75cad88b199f45d5bab5f61446be107f2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88508-whttps://doaj.org/toc/2045-2322Abstract The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17β-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer.Rahel KlossnerMichael GroesslNadine SchumacherMichaela FuxGeneviève EscherSophia VeroutiHeidi JaminBruno VogtMarkus G. MohauptCarine Gennari-MoserNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rahel Klossner Michael Groessl Nadine Schumacher Michaela Fux Geneviève Escher Sophia Verouti Heidi Jamin Bruno Vogt Markus G. Mohaupt Carine Gennari-Moser Steroid hormone bioavailability is controlled by the lymphatic system
description	Abstract The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17β-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer.
format	article
author	Rahel Klossner Michael Groessl Nadine Schumacher Michaela Fux Geneviève Escher Sophia Verouti Heidi Jamin Bruno Vogt Markus G. Mohaupt Carine Gennari-Moser
author_facet	Rahel Klossner Michael Groessl Nadine Schumacher Michaela Fux Geneviève Escher Sophia Verouti Heidi Jamin Bruno Vogt Markus G. Mohaupt Carine Gennari-Moser
author_sort	Rahel Klossner
title	Steroid hormone bioavailability is controlled by the lymphatic system
title_short	Steroid hormone bioavailability is controlled by the lymphatic system
title_full	Steroid hormone bioavailability is controlled by the lymphatic system
title_fullStr	Steroid hormone bioavailability is controlled by the lymphatic system
title_full_unstemmed	Steroid hormone bioavailability is controlled by the lymphatic system
title_sort	steroid hormone bioavailability is controlled by the lymphatic system
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/75cad88b199f45d5bab5f61446be107f
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Steroid hormone bioavailability is controlled by the lymphatic system

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