Besides taste buds, several other tissues express taste receptors (TR), where these exert various non-gustatory functions, e.g. in immunity, metabolism, endocrinology and/or reproduction. Human skin expresses the bitter TR, TAS2R4, whose functions in skin biology remain unknown. Since we show here that the epithelium of human scalp hair follicles (HFs) prominently and hair cycle-dependently expresses functional TAS2R4, we have explored these human chemosensory (mini-)organs as accessible model systems to dissect non-classical TR functions in human tissue physiology. In organ-cultured HFs, TAS2R4 activation by the sweet-tasting steviol-glycoside, rebaudioside A (Reb A), significantly inhibits proliferation of hair matrix keratinocytes and induces premature HF involution (catagen) ex vivo by increasing expression of the key catagen-promoting growth factor, TGF-β2, and by stimulating TGF-β signaling-related pathways/target genes such as RET-Rai and SHC3-GAB1 complexes (RNAseq). Instead, TGF-β1-3 neutralization antagonizes premature catagen induction by Reb A, while intrafollicular TAS2R4 knockdown by transient TAS2R4 siRNA transfection of HFs ex vivo in the presence of excess Reb A maintains anagen. This confirms that hair growth inhibition by Reb A is indeed mediated by TAS2R4 activation and mainly driven by TGF-β pathway activation. Using the cycling human scalp HF and TAS2R4 as clinically relevant, instructive, and experimentally pliable model systems, this introduces TRs as chemosensory regulators of human organ/tissue remodeling. Specifically, we identify a novel, drug-free strategy for the therapeutic inhibition of unwanted hair growth (incl. hypertrichosis, hirsutism) by topically applicable tastants, such as steviol-glycoside TAS2R4 agonists.

ESDR571 - Human Hair Follicles can “Taste”: Stimulation of the Bitter Taste Receptor TAS2R4 Inhibits Hair Growth Ex Vivo by Up-Regulating TGF-β2

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.