P40 RETINOIC ACID INDUCES CATAGEN BY TGF-ß2 UPREGULATION IN HUMAN HAIR FOLLICLES IN VITRO

¹Tanja Spexard, ¹Ralf Paus, ²Ursula Halsner, ²Sibylle Eberle, ¹Karoline Krause, ¹Ingrid Moll und ¹Kerstin Foitzik. ¹Department of Dermatology, Univ. Hosp. Eppendorf, Hamburg, Germany, ²ArteMedicMeditra GmbH, Gräfelfing, Germany

Retinoic acid can have adverse effects on human hair follicles. While systemic intake of retinoic acid is able to induce telogen effluvium, topical treatment of human scalp hair follicles with tretinoin may also result in a prolonged anagen phase. Therefore, we have investigated the influence of all-trans retinoic acid (RA) on the growth of human hair follicles in culture.

Human anagen hair follicles were dissected, and organ-cultured in supplemented Williams E Medium for 2, 4 or 6 days with retinoic acid (10-8, 10-11 M), and length of the hair shaft was measured every second day, before follicles were embedded for cryosectioning. Hair shaft length decreased already significantly after two days in the RA-treated group, compared to control. Staging of the hair follicles showed that approx. 80% of the RA-treated hair follicles at day 6 had entered catagen, compared to 30% of catagen follicles in the control group. This corresponded to a relative upregulation of TUNEL⁺ cells and a downregulation of Ki67⁺ cells in the RA-treated follicles. Since TGF-ß2 has recently been implicated as an inducer of catagen in human hair follicles, we next studied whether RA treatment had any affect on follicular TGF-ß2 expression. TGF-ß2 immunoreactivity was detected in the outer root sheath (ORS) of normal, untreated anagen VI scalp hair follicles. The lower portion of the hair bulb and the dermal papilla were negative for TGF-ß2. In catagen follicles, TGF-ß2 was also expressed in the regressing epithelial strand. After 4 days of RA treatment, TGF-ß2 was significantly upregulated in anagen hair follicles in the dermal papilla and the dermal sheath. In addition, the intensity of TGF-ß1 and TGF-ß receptor type II (TGFRII) immunoreactivity was increased in the ORS of RA-treated hair follicles, compared to control. We demonstrated that RA is indeed capable of inducing catagen in human hair follicles in vitro and that RA upregulates TGF-ß2 in the dermal papilla and TGFRII expression in the ORS. This shows that RA can induce catagen, possibly via induction of TGF-ß2 and upregulation of its receptor.