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

Abstract

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