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Testosterone‐androgen receptor: The steroid link inhibiting TRPM8‐mediated cold sensitivity
Author(s) -
Gkika Dimitra,
Lolignier Stéphane,
Grolez Guillaume P.,
Bavencoffe Alexis,
Shapovalov Georges,
Gordienko Dmitri,
Kondratskyi Artem,
Meleine Mathieu,
Prival Laetitia,
Chapuy Eric,
Etienne Monique,
Eschalier Alain,
Shuba Yaroslav,
Skryma Roman,
Busserolles Jérôme,
Prevarskaya Natalia
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902270r
Subject(s) - trpm8 , transient receptor potential channel , androgen receptor , testosterone (patch) , chemistry , receptor , androgen , dorsal root ganglion , endocrinology , cold sensitivity , medicine , microbiology and biotechnology , sensory system , biology , prostate cancer , biochemistry , hormone , trpv1 , neuroscience , mutant , cancer , gene
Recent studies have revealed gender differences in cold perception, and pointed to a possible direct action of testosterone (TST) on the cold‐activated TRPM8 (Transient Receptor Potential Melastatin Member 8) channel. However, the mechanisms by which TST influences TRPM8‐mediated sensory functions remain elusive. Here, we show that TST inhibits TRPM8‐mediated mild‐cold perception through the noncanonical engagement of the Androgen Receptor (AR). Castration of both male rats and mice increases sensitivity to mild cold, and this effect depends on the presence of intact TRPM8 and AR. TST in nanomolar concentrations suppresses whole‐cell TRPM8‐mediated currents and single‐channel activity in native dorsal root ganglion (DRG) neurons and HEK293 cells co‐expressing recombinant TRPM8 and AR, but not TRPM8 alone. AR cloned from rat DRGs shows no difference from standard AR. However, biochemical assays and confocal imaging reveal the presence of AR on the cell surface and its interaction with TRPM8 in response to TST, leading to an inhibition of channel activity.