TRANSFORMING-GROWTH-FACTOR-BETA RECEPTOR-TYPE-I AND TYPE-II EXPRESSION DURING MURINE HAIR FOLLICLE DEVELOPMENT AND CYCLING

Although the TGF-beta family of growth factors probably regulates skin and hair follicle development, its exact role is still quite ill-defi ned. Here, we characterize the correlative expression pattern of the i nterdependent high affinity receptor proteins for TGF-beta 1 and TGF-b eta 3, TGF-beta receptor type I (TGF-beta RI) and TGF-beta receptor ty pe II (TGF-beta RII), during hair follicle development and cycling in C57BL/6 mice. During neonatal follicle development, TGF-beta RII immun oreactivity is confined to epithelial cells. Focal epidermal TGF-beta RII expression is seen even before actual hair placode formation. In c ontrast to the TGF-beta RII immunoreactivity in the outer root sheath, precortical hair matrix and inner root sheath cells were TGF-beta RII negative during hair bulb morphogenesis. TGF-beta RI (Alk-5) immunore activity largely overlapped the TGF-beta RII expression pattern, but w as more wide-spread, During hair follicle cycling in adolescent mice, TGF-beta RII immunoreactivity was restricted to follicles, and was str ikingly hair cycle dependent (maximal immunoreactivity: anagen VI and early catagen). Again, TGF-beta RI (Alk-5) immunoreactivity co-localiz ed with TGF-beta RII immunoreactivity, but was more extensive. Reverse transcriptase polymerase chain reaction analysis of TGF-beta RII mRNA confirmed peak transcript levels in back skin with most hair follicle s in the anagen VI-catagen transformation. mRNA levels of TGF-beta RI (Alk-5) did not vary significantly during the hair cycle, whereas thos e of TGF-beta RI (threonine-serine kinase 7 L) declined during early a nagen, and were maximal during the anagen-catagen transition. This pro vides a basis for defining the choreography of TGF-beta-related signal ling during hair follicle morphogenesis and cycling, introduces intrae pidermal TGF-beta RII immunoreactivity as a marker for imminent follic le development, and supports the concept that both TGF-beta RII and TG F-beta RI stimulation is involved in, but not restricted to, the contr ol of catagen induction.