P-10   THE SYNERGISTIC EFFECT OF MINOXIDIL IN COMBINATION WITH ALL-TRANS-RETINOIC ACID (TRETINOIN) ON HAIR GROWTH

YJ Oh, JH Han, OS Kwon, JH Chung, KH Cho, HC Eun, KH Kim Department of Dermatology, Seoul National University Hospital, Seoul, Korea.

Simultaneous administration of topical minoxidil with tretinoin may enhance the response of androgenetic alopecia (AGA) to minoxidil. Possible mechanisms include epithelial and vascular proliferation and increased minoxidil absorption through alteration of the stratum corneum barrier. Recent study shows that co-treatment with tretinoin resulted in a threefold increase in cutaneous minoxidil absorption compared with a control vehicle without observed side effects. In this study, we studied if co-treatment of retinoic acid (RA) can enhance the hair growing effect of minoxidil and the mechanisms how the hair growth was stimulated. We tried to elucidate the mechanisms of hair growth by investigating the expressions of Erk, Akt, bcl-2, bax, p53, p21, and PCNA in cultured human dermal papilla cells (DPCs) as evaluated by Western blot analyses. Our study shows that the levels of Erk phosphorylation and phosphorylated Akt increased significantly 1 h post-treatment with minoxidil together with RA versus control, minoxidil or RA alone. The level of bcl-2 increased significantly 1 h post-treatment with minoxidil together with RA versus control, minoxidil or RA alone, while the level of bax decreased significantly. The levels of p53 and p21 decreased significantly 1 h post-treatment with minoxidil together with RA versus control, minoxidil or RA alone. However, the level of PCNA increased significantly 1 h post-treatment with minoxidil together with RA versus control, minoxidil or RA alone. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil together with RA. Our data suggest that RA act synergistically with minoxidil and may promote cell proliferation of human DPCs by activating both Erk and Akt signaling and by preventing cell death processes by increasing the ratio of Bcl-2/Bax.