Minoxidil is the most used drug with proved effects in the treatment of androgenetic alopecia (AGA), but little is known about its pharmacological activity and target cells in hair follicles. As AGA is characterized by follicle atrophy, accelerated hair cycles and hair fiber thinning, we postulated that kerati-nocyte proliferation/differentiation is affected and we tested Minoxidil’s effects on those parameters. Normal human keratinocytes (NHK) of follicular or epidermal origin were cultured in the presence of Minoxidil (0, 0.1, 1, 10, 100, 1,000 μM) during 5-8 days in various media (high-/low-calcium content, with or without serum). Proliferation was assessed by mitochondrial dehydrogenase activity (XTT), BrdU incorporation, lysosome numeration (neutral red incorporation) and total protein dosage. Drug-induced cytotoxicity was measured by lactate dehydrogenase release in culture supernatant, and pro-differentiating effects were evaluated by relative involucrin expression (ELISA dosage). On this basis, we showed that Minoxidil had biphasic effects on the proliferation and differentiation of NHK: Minoxidil stimulated NHK proliferation at micromolar doses, while antiproliferative, pro-differentiative and partially cyto-toxic effects were observed with millimolar concentrations. We can hypothesize that Minoxidil hypertrichotic activity in vivo is possibly mediated by the maintenance of proliferative potential in follicular keratinocytes precociously committed to differentiation.

Keywords:
Androgenetic alopecia, Minoxidil, Normal human keratinocytes, proliferation differentiation, Follicular keratinocytes
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© 1997 S. Karger AG, Basel
1997
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