ABSTRACT
The purpose of this study was to evaluate human hair follicle melanogenic activity using the [14C]-2-thiouracil, which was known to incorporate into nascent melanins. Results obtained on pigmented, grey and non-pigmented hair follicles demonstrated that [(14)C]-2-TU incorporation was restricted to the melanogenic compartment with a strong accumulation located around dermal papilla and within the fibre of pigmented hair follicles. Quantitative analysis of [(14)C]-2-TU incorporation showed a significant increase in pigmented hair follicles upon stimulation with 1 microm forskolin concomitant to an increase in tyrosinase levels. A strong significant decrease in [14C]-2-TU incorporation was noted, when hair follicles were incubated with the tyrosinase competitive inhibitor kojic acid (200 microm). Incubation with the MC1-R agonist alpha-MSH (0.2 microm) did not induce a significant stimulation of hair melanogenesis. The present model could thus represent a useful new tool to identify modulators of human hair pigmentation.
Subject(s)
Hair Follicle/metabolism , Melanins/metabolism , Skin Pigmentation/physiology , Thiouracil/metabolism , Biopsy , Carbon Radioisotopes , Colforsin/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism , Enzyme Inhibitors/pharmacology , Female , Hair Follicle/drug effects , Hair Follicle/pathology , Humans , Middle Aged , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Pyrones/pharmacology , Receptor, Melanocortin, Type 1/agonists , Skin Pigmentation/drug effects , alpha-MSH/pharmacologyABSTRACT
NAD(+) dependent 15-hydroxyprostaglandin dehydrogenate (15-PGDH) catalyses oxidation of 15(S)-hydroxyl group of prostaglandins and as a result inactivates their physiological potential. Positive effects of prostaglandins or prostaglandin analogues were reported on terminal hair, vellus hair or eyelash growth and a complex prostaglandin network was recently described in human hair follicle. In the present study, we showed that 15-PGDH was expressed in human hair follicle mainly in melanocytes and keratinocytes, which brought us to consider this enzyme as a possible target to sustain local prostaglandin production. Using a recombinant enzymatic strategy, specific 15-PGDH inhibitors were screened. We identified a thiazolidine dione derivative exhibiting efficacy on follicular outer root sheath keratinocytes, since it concomitantly decreased the production of deactivated 13,14 dihydro 15-ketoprostaglandin F(2alpha) and sustained prostaglandin F(2alpha)in vitro production. In the context of recent interest in prostaglandins and prostaglandin analogues as hair regrowth agents, we postulated that the use of selected 15-PGDH inhibitors could reinforce or prolong the effect of these physiological mediators on hair and skin.