Control of murine hair follicle regression (catagen) by TGF-beta 1 in vivo

The regression phase of the hair cycle (catagen) is an apoptosis-driven pro cess accompanied by terminal differentiation, proteolysis, and matrix remod eling. As an inhibitor of keratinocyte proliferation and inductor of kerati nocyte apoptosis, transforming growth factor beta 1 (TGF-beta 1) has been p roposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta 1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the pot ential involvement of TGF-beta 1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta 1 null mi ce and age-matched wild-type littermates, and assessed the effects of TGF-b eta 1 injection on murine anagen hair follicles in vivo. At day 18 p.p., ha ir follicles in TGF-beta 1 -/- mice were still in early catagen, whereas ha ir follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta 1 -/- mice displayed more Ki-67-positive cells an d fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta 1 into the back skin of mice induced prema ture catagen development. In addition, the number of proliferating follicle keratinocytes was reduced and the number of TUNEL + cells was increased in the TGF-beta 1-treated mice compared to controls. Double visualization of TGF-beta type II receptor (TGFRII) and TUNEL reactivity revealed colocaliza tion of apoptotic nuclei and TGFRII in catagen follicles. These data strong ly support that TGF-beta 1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte pro liferation and induction of apoptosis. Thus, TCF-beta RII agonists and anta gonists may provide useful therapeutic tools for human hair growth disorder s based on premature or retarded catagen development (effluvium, alopecia, hirsutism).