Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

David Møbjerg Kristensen, Christèle Desdoits-Lethimonier, Abigail L Mackey, Marlene Danner Dalgaard, Federico De Masi, Cecilie Hurup Munkbøl, Bjarne Styrishave, Jean-Philippe Antignac, Bruno Le Bizec, Christian Platel, Anders Hay-Schmidt, Tina Kold Jensen, Laurianne Lesné, Séverine Mazaud-Guittot, Karsten Kristiansen, Søren Brunak, Michael Kjaer, Anders Juul, Bernard Jégou

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

103 Downloads (Pure)

Resumé

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind115
Udgave nummer4
Sider (fra-til)E715-E724
ISSN0027-8424
DOI
StatusUdgivet - 23. jan. 2018

Fingeraftryk

Hypogonadism
Ibuprofen
Luteinizing Hormone
Western World
Endocrine System
Leydig Cells
Sertoli Cells
Endocrinology
Clinical Trials
Cell Line

Citer dette

Kristensen, D. M., Desdoits-Lethimonier, C., Mackey, A. L., Dalgaard, M. D., De Masi, F., Munkbøl, C. H., ... Jégou, B. (2018). Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proceedings of the National Academy of Sciences of the United States of America, 115(4), E715-E724. https://doi.org/10.1073/pnas.1715035115
Kristensen, David Møbjerg ; Desdoits-Lethimonier, Christèle ; Mackey, Abigail L ; Dalgaard, Marlene Danner ; De Masi, Federico ; Munkbøl, Cecilie Hurup ; Styrishave, Bjarne ; Antignac, Jean-Philippe ; Le Bizec, Bruno ; Platel, Christian ; Hay-Schmidt, Anders ; Jensen, Tina Kold ; Lesné, Laurianne ; Mazaud-Guittot, Séverine ; Kristiansen, Karsten ; Brunak, Søren ; Kjaer, Michael ; Juul, Anders ; Jégou, Bernard. / Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. I: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Bind 115, Nr. 4. s. E715-E724.
@article{920ca2212f6f45e782c7bc0b7898ed7d,
title = "Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism",
abstract = "Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named {"}compensated hypogonadism,{"} a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.",
keywords = "Adult, Analgesics, Non-Narcotic/adverse effects, Cell Line, Gene Expression/drug effects, Humans, Hypogonadism/blood, Ibuprofen/adverse effects, In Vitro Techniques, Leydig Cells/drug effects, Luteinizing Hormone/blood, Male, Middle Aged, Prostaglandins/biosynthesis, Sertoli Cells/drug effects, Testosterone/blood",
author = "Kristensen, {David M{\o}bjerg} and Christ{\`e}le Desdoits-Lethimonier and Mackey, {Abigail L} and Dalgaard, {Marlene Danner} and {De Masi}, Federico and Munkb{\o}l, {Cecilie Hurup} and Bjarne Styrishave and Jean-Philippe Antignac and {Le Bizec}, Bruno and Christian Platel and Anders Hay-Schmidt and Jensen, {Tina Kold} and Laurianne Lesn{\'e} and S{\'e}verine Mazaud-Guittot and Karsten Kristiansen and S{\o}ren Brunak and Michael Kjaer and Anders Juul and Bernard J{\'e}gou",
note = "Copyright {\circledC} 2018 the Author(s). Published by PNAS.",
year = "2018",
month = "1",
day = "23",
doi = "10.1073/pnas.1715035115",
language = "English",
volume = "115",
pages = "E715--E724",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "4",

}

Kristensen, DM, Desdoits-Lethimonier, C, Mackey, AL, Dalgaard, MD, De Masi, F, Munkbøl, CH, Styrishave, B, Antignac, J-P, Le Bizec, B, Platel, C, Hay-Schmidt, A, Jensen, TK, Lesné, L, Mazaud-Guittot, S, Kristiansen, K, Brunak, S, Kjaer, M, Juul, A & Jégou, B 2018, 'Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism', Proceedings of the National Academy of Sciences of the United States of America, bind 115, nr. 4, s. E715-E724. https://doi.org/10.1073/pnas.1715035115

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. / Kristensen, David Møbjerg; Desdoits-Lethimonier, Christèle; Mackey, Abigail L; Dalgaard, Marlene Danner; De Masi, Federico; Munkbøl, Cecilie Hurup; Styrishave, Bjarne; Antignac, Jean-Philippe; Le Bizec, Bruno; Platel, Christian; Hay-Schmidt, Anders; Jensen, Tina Kold; Lesné, Laurianne; Mazaud-Guittot, Séverine; Kristiansen, Karsten; Brunak, Søren; Kjaer, Michael; Juul, Anders; Jégou, Bernard.

I: Proceedings of the National Academy of Sciences of the United States of America, Bind 115, Nr. 4, 23.01.2018, s. E715-E724.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

AU - Kristensen, David Møbjerg

AU - Desdoits-Lethimonier, Christèle

AU - Mackey, Abigail L

AU - Dalgaard, Marlene Danner

AU - De Masi, Federico

AU - Munkbøl, Cecilie Hurup

AU - Styrishave, Bjarne

AU - Antignac, Jean-Philippe

AU - Le Bizec, Bruno

AU - Platel, Christian

AU - Hay-Schmidt, Anders

AU - Jensen, Tina Kold

AU - Lesné, Laurianne

AU - Mazaud-Guittot, Séverine

AU - Kristiansen, Karsten

AU - Brunak, Søren

AU - Kjaer, Michael

AU - Juul, Anders

AU - Jégou, Bernard

N1 - Copyright © 2018 the Author(s). Published by PNAS.

PY - 2018/1/23

Y1 - 2018/1/23

N2 - Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

AB - Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

KW - Adult

KW - Analgesics, Non-Narcotic/adverse effects

KW - Cell Line

KW - Gene Expression/drug effects

KW - Humans

KW - Hypogonadism/blood

KW - Ibuprofen/adverse effects

KW - In Vitro Techniques

KW - Leydig Cells/drug effects

KW - Luteinizing Hormone/blood

KW - Male

KW - Middle Aged

KW - Prostaglandins/biosynthesis

KW - Sertoli Cells/drug effects

KW - Testosterone/blood

UR - https://doi.org/10.1073/pnas.1805313115

U2 - 10.1073/pnas.1715035115

DO - 10.1073/pnas.1715035115

M3 - Journal article

VL - 115

SP - E715-E724

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 4

ER -