Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

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FASEB J 2002 Dec;16(14):1967-9

Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

Br J Dermatol 2002 Aug;147(2):222-9

Langerhans cells that express matrix metalloproteinase 9 increase in human dermis during sensitization to diphenylcyclopropenone in patients with alopecia areata.

BACKGROUND: We know little of the initial events during the sensitization phase of contact allergy in humans. Alopecia areata (AA), a disease of unknown pathogenesis characterized by patchy hair loss, may be treated by inducing contact allergy to diphenylcyclopropenone (DPC), later followed by its topical application. OBJECTIVES: To learn more about the initial events during sensitization in human skin, we studied the early events during induction of contact allergy to DPC in patients with AA. METHODS: DPC 2% and sodium lauryl sulphate (SLS) 4% were applied on the backs of eight patients with AA. Punch biopsies were taken 6 and 24 h after application. The biopsies were snap-frozen and cryostat sections were evaluated with immunohistochemistry using antibodies against CD1a, HLA-DR, CD3, CD54 and matrix metalloproteinase 9 (MMP-9). RESULTS: After 24 h all subjects exhibited erythema on the DPC-treated areas. Histological evaluation of biopsies from these areas showed hydropic degeneration and a significantly increased number of MMP-9+ cells in the dermis (P < 0.0005). The MMP-9+ cells were identified with double immunofluorescence staining as CD1a + Langerhans cells. The expression of the other markers studied remained unaltered irrespective of treatment, including treatment with SLS. CONCLUSIONS: Our findings show that DPC induces an irritant reaction leading to an increased number of MMP-9+ CD1a+ cells in the dermis during the initial phase of sensitization.

Rev Med Chir Soc Med Nat Iasi 2001 Jul-Sep;105(3):533-5

Endocrinological disorders in association with alopecia areata-a 27 patients study

Alopecia areata is a dermatological disease, characterized by the loss of hair, which affect men, women and children and can evaluate alone or in association with a variety of other disorders. Between these endocrinological diseases, especial thyroid disorders, have a high incidence. Twenty-seven patients with alopecia areata (12 women and 15 men) aged between 3 and 46 years were endocrinologically investigated. Eighteen of them (66.6%) had endocrinological disorders. Thyroid diseases were present in 10 cases (37%): 4 cases with endemic goiter, 2 cases with nodular goiter and 4 cases with hypothyroidism (1 case with autoimmune thyroiditis, 1 case with nodular goiter, 1 case with cystic goiter and 1 case with hypothyroidism post thyroidectomy for thyroidal lymphoma). Twelve cases (44.4%) were found with tetania. The incidence of thyroid diseases in alopecia areata is higher then in general population (2%), as well as the incidence of tetania. These evidences suggest that it is necessary to make a screening of endocrinological disorders in patients with alopecia areata.

J Am Acad Dermatol 2001 Sep;45(3 Suppl):S81-6

Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss.

In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla.

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