title: Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin.
abstract: The presence of 5 alpha-reductase (5 alpha-R) in skin may indicate that the androgen regulation of sebaceous glands and sebum production requires 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, scalp, and non-acne-prone areas; to determine if 5 alpha-R activity is concentrated in sebaceous glands; to assess whether there are regional differences in this enzyme's activity; and to test the effects of azasteroid inhibitors and 13-cis retinoic acid on 5 alpha-R in these tissues. Sebaceous glands were microdissected from facial skin, scalp, and non-acne-prone skin (arm, breast, abdomen, leg), and the activity of 5 alpha-R was determined. A total of 49 samples from 23 male and 21 female subjects without acne (age range, 16 to 81 years, 56 +/- 20 years [mean +/- 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 alpha-R activity was significantly higher in the sebaceous glands compared 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 amount of sebaceous gland material obtained from non-acne-prone areas (32 +/- 6 [mean +/- SEM]), 35 +/- 7 (mean +/- SEM) versus 6.0 +/- 3.0 (mean +/- SEM) pmol/min/mg protein, p = 0.014 and 0.007, respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the enzyme 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 concentrated in sebaceous glands and is significantly higher in sebaceous glands from the face and scalp compared to non-acne-prone areas, and the action 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 of the type 1 5 alpha-R may offer a viable approach to the management of sebum production and, hence, acne.
authors.affiliation: Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.
authors.forename: D
authors.initials: D
authors.lastname: Thiboutot
authors.forename: G
authors.initials: G
authors.lastname: Harris
authors.forename: V
authors.initials: V
authors.lastname: Iles
authors.forename: G
authors.initials: G
authors.lastname: Cimis
authors.forename: K
authors.initials: K
authors.lastname: Gilliland
authors.forename: S
authors.initials: S
authors.lastname: Hagari
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001378:Azasteroids / Q000494:pharmacology; D042944:Cholestenone 5 alpha-Reductase; D005145:Face; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015474:Isotretinoin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012535:Scalp; D012627:Sebaceous Glands / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D042944:Cholestenone 5 alpha-Reductase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D015474:Isotretinoin