P29 HAIR GROWTH CONTROL BY FOLLISTATIN

¹Nakamura M., ¹Foitzik K., ²Matzuk M., ³Halsner U., ³Eberle S., ¹Paus R. ¹Dept. of Dermatology, University Hospital Eppendorf, Hamburg, Germany; ²Dept.of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics, Baylor College of Medicine, Texas, USA; ³Artemedic-Meditra, München, Germany.

Members of  the TGF-b/BMP family are involved in the control of hair follicle morphogenesis and cycling. The activity of several members of this family (activin, BMP-2, 4, 7) is usually antagonized by follistatin. Since both follistatin-deficient and activin knockout mice show abnormalities in whisker development, we have further explored the role of follistatin in hair follicle development and/or cycling. Compared to wild type controls, follistatin knockout mice showed a significant retardation of hair follicle morphogenesis. However, immunohistological analysis of proliferating cell antigen (Ki67), apoptotic cells (TUNEL), selected adhesion molecules (NCAM), morphogens (KGF), or growth factor receptors (m-met, TGFbR-II, FGFR-2) failed to reveal any substantial differences between knockout mice and wild-type controls. In adult human scalp skin, follistatin immunoreactivity was seen in the ORS of anagen VI hair follicles as well as in the interfollicular epidermis. In organ culture of human anagen VI scalp hair follicles, recombinant human follistatin inhibited hair shaft elongation and induced  premature hair follicle regression (catagen), along with an increase of TUNEL⁺ apoptotic cells. Semi-quantitative RT-PCR showed that steady-levels of follistatin mRNA in murine back skin (C57BL/6) declined during anagen (compared to telogen), but significantly increased in skin with all hair follicles in catagen and telogen. Taken together, these data are consistent with the concept that follistatin is involved in murine and human hair growth control, both during hair follicle development and cycling, likely by interactions with BMPs and/or activin.