071 Transcriptional Regulation of Type II 5á-Reductase in Human Dermal Papilla Cells

Jotaro Nakanishi and Toshihiko Hibino. Shiseido Life Science Research Center, Yokohama, Japan.

Previous studies suggested that type II 5alpha-reductase (5aRII) contributed to androgenetic hair loss. This was supported by the facts that 1) androgenetic alopecia is not observed in patients with 5aRII deficiency, and 2) finasteride, a specific inhibitor of 5aRII, is effective on the treatment of androgenetic alopecia. In spite of its importance, regulatory mechanism of 5aRII is still unclear. In this study, we tried to find out the transcriptional regulation of 5aRII in human dermal papilla cells (hDPCs). First, we isolated a genomic clone containing 6-kb of the 5’-flanking region of 5aRII gene from a human genomic library. In the immediate upstream sequence from the transcription start site between –1 to –200, there are three GC-boxes resembling recognition sites for Sp1/Sp3, but no TATA or CAAT sequences. Analysis of the promoter activity revealed that the second GC-box at –47/–42 was responsible for the minimal promoter activity. Although there are many candidate molecules to control the transcriptional activity of 5aRII, we focused on SRY (sex-determining region Y), a male specific transcriptional factor. Within the –2400/–1850 region, multiple SRY binding sites were obserbed. The mRNA level of 5aRII was in proportion to the expression level of SRY in hDPCs from beard and frontal scalp with androgenetic alopecia. To confirm the function of SRY, hDPCs were transfected with SRY expression plasmid. The expression of 5aRII in the transfected cells was remarkably stimulated as compared with control cells. These results suggest that SRY is a male-specific transcriptional stimulator for 5aRII in hDPCs.