ACTIVITY OF THE TYPE-1 5-ALPHA-REDUCTASE EXHIBITS REGIONAL DIFFERENCES IN ISOLATED SEBACEOUS GLANDS AND WHOLE SKIN

The presence of 5 alpha-reductase (5 alpha-R) in skin may indicate tha t the androgen regulation of sebaceous glands and sebum production req uires the local conversion of testosterone to dihydrotestosterone. The goals of this study were to identify which isozyme of 5 alpha-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scal p, and non-acne-prone areas; to determine if 5 alpha-R activity is con centrated in sebaceous glands; to assess whether there are regional di fferences in this enzyme's activity; and to test the effects of azaste roid inhibitors and 13-cis retinoic acid on 5 alpha-R in these tissues . Sebaceous glands were microdissected from facial skin, scalp, and no n-acne-prone skin (arm, breast, abdomen, leg), and the activity of 5 a lpha-R was determined. A total of 49 samples from 23 male and 21 femal e subjects without acne (age range, 16 to 81 years, 56 +/- 20 years [m ean +/- SD]) was analyzed. The biochemical properties of the enzyme in each of the samples tested are consistent with those of the type 1 5 alpha-R. Minimal to no type 2 5 alpha-R was detected. The level of 5 a lpha-R activity was significantly higher in the sebaceous glands compa red to whole skin in facial skin (p 0.047), scalp (p = 0.039), and non -acne-prone skin (p = 0.04). Enzyme activity in sebaceous glands from facial skin and scalp was significantly higher than in a comparable am ount of sebaceous gland material obtained from non-acne-prone areas (3 2 +/- 6 [mean +/- SEM]), 35 +/- 7 (mean +/- SEM) versus 6.0 +/- 3.0 (m ean +/- SEM) pmol/min/mg protein, p = 0.014 and 0.007, respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the enzym e with 50% inhibitory concentration values greater than 500 nM. These data demonstrate that in the skin from older patients without acne the type 1 isozyme of 5 alpha-R predominates, its activity is concentrate d in sebaceous glands and is significantly higher in sebaceous glands from the face and scalp compared to non-acne-prone areas, and the acti on of 13-cis retinoic acid in the control of acne is not at the level of 5 alpha-R. Furthermore, we suggest that specific inhibition ofthe t ype 1 5 alpha-R may offer a viable approach to the management of sebum production and, hence, acne.