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This is an abstract, mail me if you want the entire PDF.
Summary 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-b2 (TGF-b2) in dermal papilla cells. TGF-b2 suppresses proliferation
of epithelial cells and stimulates synthesis of certain caspases. Then TGF-b2
triggers the intrinsic caspase network and subsequently epithelial cells are eliminated
through apoptotic cell death. TGF-b antagonists are effective in preventing catagenlike
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-
a-reductase; (2) the synthesis of TGF-b2 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.
4. TGF-b antagonists promote hair
growth
4.1. Suppression of TGF-b is effective for
preventing catagen progression
If TGF-b is responsible for the induction of catagen,
suppression of TGF-b could prevent entry into catagen
or progression of catagen.
First of all, the effect of TGF-b2 on elongation
was obvious in cultured hair follicles. Hair elongation
was suppressed in the presence of TGF-b2, in a
dose-dependent fashion [35]. When anti-TGF-b neutralizing
antibody was applied to the organ culture
system, hair growth was significantly stimulated. In
addition, fetuin, which has a TGF-b receptor-like
ligand binding domain and works as an antagonist of
TGF-b activity [44], had a similar effect to the
neutralizing antibody. In the presence of fetuin,
hair growth was markedly and significantly stimulated
[35].
A screening method for TGF-b suppression can be
developed by monitoring the level of plasminogen
activator inhibitor-1 (PAI-1), which is an early
response gene for TGF-b in many cell types [45].
Extensive screening of plant extracts showed that
hydrangea extract was able to suppress TGF-b
action. Using an organ culture system, the effect
of hydrangea extract on hair growth was examined
[36]. The extract resulted in prolonged hair growth
compared to the control, suggesting suppression of
catagen entry. Caspase activation was also suppressed
in the presence of the extract.
Summary 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-b2 (TGF-b2) in dermal papilla cells. TGF-b2 suppresses proliferation
of epithelial cells and stimulates synthesis of certain caspases. Then TGF-b2
triggers the intrinsic caspase network and subsequently epithelial cells are eliminated
through apoptotic cell death. TGF-b antagonists are effective in preventing catagenlike
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-
a-reductase; (2) the synthesis of TGF-b2 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.
4. TGF-b antagonists promote hair
growth
4.1. Suppression of TGF-b is effective for
preventing catagen progression
If TGF-b is responsible for the induction of catagen,
suppression of TGF-b could prevent entry into catagen
or progression of catagen.
First of all, the effect of TGF-b2 on elongation
was obvious in cultured hair follicles. Hair elongation
was suppressed in the presence of TGF-b2, in a
dose-dependent fashion [35]. When anti-TGF-b neutralizing
antibody was applied to the organ culture
system, hair growth was significantly stimulated. In
addition, fetuin, which has a TGF-b receptor-like
ligand binding domain and works as an antagonist of
TGF-b activity [44], had a similar effect to the
neutralizing antibody. In the presence of fetuin,
hair growth was markedly and significantly stimulated
[35].
A screening method for TGF-b suppression can be
developed by monitoring the level of plasminogen
activator inhibitor-1 (PAI-1), which is an early
response gene for TGF-b in many cell types [45].
Extensive screening of plant extracts showed that
hydrangea extract was able to suppress TGF-b
action. Using an organ culture system, the effect
of hydrangea extract on hair growth was examined
[36]. The extract resulted in prolonged hair growth
compared to the control, suggesting suppression of
catagen entry. Caspase activation was also suppressed
in the presence of the extract.
