Role of TGF-beta2 in the human hair cycle.

Male pattern baldness is the result of premature entry into catagen due to androgens. In order to prevent hair loss, it is important to understand two critical steps, i.e., the induction mechanism of premature entry and the regression process of catagen. At the initiation, dihydrotestosterone (DHT) stimulates synthesis of transforming growth factor-beta2 (TGF-beta2) in dermal papilla cells. TGF-beta2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. Then TGF-beta2 triggers the intrinsic caspase network and subsequently epithelial cells are eliminated through apoptotic cell death. TGF-beta antagonists are effective in preventing catagen-like morphological changes and in promoting elongation of hair follicles in vivo and in vitro. These lines of evidence strongly suggest the presence of a "catagen cascade" in male pattern baldness, involving: (1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network. These sequential events contribute to the shortening of the human hair cycle. Copyright 2004 Japanese Society for Investigative Dermatology