Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we report that the stress hormone corticosterone—which is derived from the adrenal gland and is the rodent equivalent of cortisol in humans—regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice. In the absence of systemic corticosterone, HFSCs enter substantially more rounds of the regeneration cycle throughout life. Conversely, under chronic stress, increased levels of corticosterone prolong HFSC quiescence and maintain hair follicles in an extended resting phase. Mechanistically, corticosterone acts on the dermal papillae to suppress the expression of Gas6, a gene that encodes the secreted factor growth arrest specific 6. Restoring Gas6 expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Our work identifies corticosterone as a systemic inhibitor of HFSC activity through its effect on the niche, and demonstrates that the removal of such inhibition drives HFSCs into frequent regeneration cycles, with no observable defects in the long-term.

慢性、持续暴露于压力源会深刻影响组织稳态，尽管这些变化发生的机制在很大程度上是未知的。在这里，我们报告称，应激激素皮质酮（源自肾上腺，相当于人类皮质醇的啮齿动物）调节小鼠毛囊干细胞 (HFSC) 静止和毛发生长。在没有全身性皮质酮的情况下，HFSCs 在整个生命过程中进入了更多轮的再生周期。相反，在慢性压力下，皮质酮水平升高会延长 HFSC 的静止期，并使毛囊维持在延长的静止期。从机制上讲，皮质酮作用于真皮乳头以抑制Gas6的表达，一种编码分泌因子生长停滞特异性 6 的基因。恢复Gas6表达克服了应激诱导的 HFSC 激活和毛发生长抑制。我们的工作通过皮质酮对生态位的影响将皮质酮确定为 HFSC 活性的系统性抑制剂，并证明去除这种抑制会促使 HFSC 进入频繁的再生周期，从长远来看没有明显的缺陷。