743 Hair follicles can “taste”: Stevioside stimulation of the bitter taste receptor, TAS2R4, inhibits human hair growth ex vivo

Besides taste buds, many other tissues express receptors (TR), where they exert various, often ill-explored non-gustatory functions, e.g. in immunity and metabolism. These evolutionary ancient functions of human TRs can be optimally interrogated skin, whose keratinocytes selected TRs, its dominant appendage, the hair follicle (HF). However, role skin physiology is unknown. Therefore, we have asked whether are expressed scalp HFs if their specific stimulation or silencing affects growth. Here, show that HF prominently cycle-dependently bitter receptor, TAS2R4 (mRNA, protein). When was stimulated organ-cultured anagen by sweet-tasting steviol-glycoside agonist, rebaudioside A (Reb A), this significantly inhibited matrix keratinocyte proliferation induced premature catagen development ex vivo. RebA effects could reversed knockdown Mechanistically, these mainly caused TAS2R4-mediated enhanced expression/ secretion key catagen-promoting growth factor, TGFβ2, since TGFß-neutralization counteracted RebA-induced induction RNAseq analysis showed upregulation TGFß-related signaling pathways. Thus, introduce here as important, ancestral chemosensory regulators physiology, (mini-)organ remodeling (=HF cycling), factor production (TGFß). We also identify a novel, drug-free, “gustatory” strategy for therapeutic inhibition unwanted (hirsutism, hypertrichosis) with natural sweetener.