Activity of the Type 1 5α-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.

A cross-sectional study on quality of life among acne vulgaris patients

“…18 This may be due to the fact that acne lesions generally occur in sebaceous gland connected with vellus hair and due to regional differences in the activity of type 1, 5-alpha reductase in isolated sebaceous glands. 19,20 In present study of 300 patients, 93 patients (31%) of patients had post inflammatory hyper pigmentation. The incidence of post inflammatory hyper pigmentation in our study was lower compared to that in earlier studies.…”

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

“…Keratinocyte hyperproliferation, which may lead to follicular obstruction and comedo formation in acne 19,20 , is inhibited by TGFb 21,22 . Likewise, TGFb decreases sebaceous gland lipid production 23 which is increased and altered in acne 24,25 . Finally, innate immune responses, elicited during microbial colonization by P. acnes 26,27 , may be modulated by TGFb 28 .…”

“…We thank Saxena Alka (London, UK); Ulrike Blume-Peytavi (Berlin, Germany); Leaca Crawford 34 ; Jana Estafan 24 …”

Role of FGFR2-signaling in the pathogenesis of acne

“…6,7 Acne-prone skin exhibits a higher androgen receptor (AR) density and higher 5α-reductase type-I activity than uninvolved skin. 8,9 Antiandrogens reduce the synthesis of sebaceous lipids and improve acne, whereas androgen-insensitive subjects who lack functional AR do not produce sebum and do not develop acne. 10,11 Elevated levels of interleukin-1α (IL-1α) have been detected in most open comedones of acne vulgaris.…”