Activity of the type 1 5α-reductase exhibits regional differences in isolated sebaceous glands and whole skin

D. Thiboutot, G. Harris, V. Iles, G. Cimis, K. Gilliland, S. Hagari

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

The presence of 5α-reductase (5α-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 5α-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5α-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 5α-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 5α-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 5α-R. Minimal to no type 2 5α-R was detected. The level of 5α-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 5α-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 5α-R. Furthermore, we suggest that specific inhibition of the type 1 5α-R may offer a viable approach to the management of sebum production and, hence, acne.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalJournal of Investigative Dermatology
Volume105
Issue number2
DOIs
StatePublished - Jan 1 1995

Fingerprint

Sebaceous Glands
Skin
Oxidoreductases
Scalp
Acne Vulgaris
Isotretinoin
Sebum
Enzyme activity
Scanning electron microscopy
Isoenzymes
Azasteroids
Enzymes
Finasteride
Dihydrotestosterone
Enzyme Inhibitors
Androgens
Testosterone
Abdomen
Inhibitory Concentration 50
Leg

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Thiboutot, D. ; Harris, G. ; Iles, V. ; Cimis, G. ; Gilliland, K. ; Hagari, S. / Activity of the type 1 5α-reductase exhibits regional differences in isolated sebaceous glands and whole skin. In: Journal of Investigative Dermatology. 1995 ; Vol. 105, No. 2. pp. 209-214.
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abstract = "The presence of 5α-reductase (5α-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 5α-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5α-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 5α-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 5α-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 5α-R. Minimal to no type 2 5α-R was detected. The level of 5α-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 5α-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 5α-R. Furthermore, we suggest that specific inhibition of the type 1 5α-R may offer a viable approach to the management of sebum production and, hence, acne.",
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Activity of the type 1 5α-reductase exhibits regional differences in isolated sebaceous glands and whole skin. / Thiboutot, D.; Harris, G.; Iles, V.; Cimis, G.; Gilliland, K.; Hagari, S.

In: Journal of Investigative Dermatology, Vol. 105, No. 2, 01.01.1995, p. 209-214.

Research output: Contribution to journalArticle

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AU - Thiboutot, D.

AU - Harris, G.

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AU - Hagari, S.

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N2 - The presence of 5α-reductase (5α-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 5α-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5α-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 5α-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 5α-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 5α-R. Minimal to no type 2 5α-R was detected. The level of 5α-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 5α-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 5α-R. Furthermore, we suggest that specific inhibition of the type 1 5α-R may offer a viable approach to the management of sebum production and, hence, acne.

AB - The presence of 5α-reductase (5α-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 5α-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5α-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 5α-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 5α-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 5α-R. Minimal to no type 2 5α-R was detected. The level of 5α-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 5α-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 5α-R. Furthermore, we suggest that specific inhibition of the type 1 5α-R may offer a viable approach to the management of sebum production and, hence, acne.

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