Identification and selective inhibition of an isozyme of steroid 5 alpha-reductase in human scalp.

Harris, G.; Azzolina, B.; Baginsky, Walter F.; Cimis, George; Rasmusson, Gary H.; Tolman, Richard L.; Raetz, Christian R. H.; Ellsworth, Kenneth

doi:10.1073/pnas.89.22.10787

Cited by 112 publications

(60 citation statements)

References 31 publications

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“…They are called 5a-R type 1 and 2 (5a-R1 and 5a-R2). Studies using specific inhibitors of 5a-R1 and 5a-R2 (finasteride) showed that 5a-R2 enzymatic activity is predominant in the urogenital sinus and in genital skin, whereas 5a-R1 is predominant in the central nervous system (only type 1), in pubic skin, in the adult scalp and in the nonsex skin of the normal male, normal women and hirsute patients (14)(15)(16)(17). However, the distribution and role of 5a-R1 is less clear.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Comparison of finasteride versus flutamide in the treatment of hirsutism

Falsetti

Gambera

Legrenzi

et al. 1999

European Journal of Endocrinology

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Objective: To compare the effectiveness of finasteride and flutamide in the treatment of hirsutism in patients with polycystic ovary syndrome (PCOS) and with idiopathic hirsutism. Design: Randomized study. Patients: One hundred and ten hirsute patients were selected: 64 women with PCOS and 46 with idiopathic hirsutism. Methods: Patients were assigned randomly to receive 5 mg finasteride once daily or 250 mg of flutamide twice daily, for 12 consecutive months. Hirsutism was evaluated at 12 months of therapy, with the Ferriman-Gallwey score and with measurement of the terminal hair diameters (mm) taken from four different body areas. Blood samples were taken for assessment of endocrine and hematochemical parameters. Side effects were monitored during the treatment. Results: Both finasteride and flutamide induced a significant decrease in the hirsutism scores and hair diameters at the end of 12 months. Finasteride reduced the Ferriman-Gallwey score by 31.4% in the PCOS cases and by 34.2% in the idiopathic hirsutism cases, and hair diameter by 27.0-34.1% in PCOS and by 29.6-37.9% in idiopathic hirsutism. Flutamide reduced the Ferriman-Gallwey score by 56.7% in PCOS and by 50.9% in idiopathic hirsutism, and hair diameter by 50.3-60.0% in PCOS and by 47.7-56.5% in idiopathic hirsutism. Flutamide did not induce hormone variations, while finasteride increased testosterone levels by 40% in PCOS and by 60% in idiopathic hirsutism and decreased 3a-androstanediol glucuronide (3a-diolG) by 66.7% in PCOS and by 69.5% in idiopathic hirsutism. No important side effects or changes in the hematochemical parameters were observed with finasteride, while two patients (3.6%) in the flutamide group expressed abnormal transaminase levels after 6 months of treatment. Dry skin also appeared significantly more with flutamide (67.3%) than with finasteride (23.6%). Conclusions: Both drugs are effective in the treatment of hirsutism but flutamide is more effective than finasteride.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Comparison of finasteride versus flutamide in the treatment of hirsutism

Falsetti

Gambera

Legrenzi

et al. 1999

European Journal of Endocrinology

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“…The boundaries of these narrow regions are listed in Table 1. Of the four genes in single gene regions, Catenin Delta-2 (CTNND2) has been shown to be overexpressed in prostate cancer (Burger et al, 2002) and Steroid 5-Alpha-Reductase (SRD5A1), which catalyses the conversion of testosterone into the more potent androgen dihydrotestosterone (Harris et al, 1992), has been shown to be overexpressed in breast cancer (Wiebe and Lewis, 2003). The Triple Functional Domain gene (TRIO) in Region A4 ( Figure 1c) and the Glial Cell Line-Derived Neurotrophic Factor gene (GDNF) in Region A6 (Figure 1d), however, have not been directly implicated in cancer and were further investigated in this study (see below).…”

Section: Novel Amplifications Defined In Cis Lesionsmentioning

confidence: 99%

Chromosome 5p aberrations are early events in lung cancer: implication of glial cell line-derived neurotrophic factor in disease progression

Garnis¹,

Davies²,

Buys³

et al. 2005

Oncogene

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Lung cancer is the most widely diagnosed malignancy in the world. Understanding early-stage disease will give insight into its pathogenesis. Despite the fact that preinvasive lesions are challenging to isolate, and often yield insufficient DNA for the analysis of multiple loci, genomic profiling of such lesions will lead to the discovery of causal genetic alterations, which may be otherwise masked by the gross instability associated with tumors. In this study, we report the identification of multiple early genetic events on chromosome 5p in lung cancer progression. Using a highresolution 5p-specific genomic array, which contains a tiling path of DNA segments for comparative genomic hybridization, nine novel minimal regions of loss and gain were discovered in bronchial carcinoma in situ (CIS) specimens. Within these regions we identified two candidate genes novel to lung cancer. The 0.27 Mbp region at 5p15.2 contains a single gene, Triple Functional Domain, which we determined to be differentially expressed in tumors. The 0.34 Mbp region at 5p13.2 contains Glial Cell Line-Derived Neurotrophic Factor (GDNF), which is a ligand for the RET oncogene product and is normally expressed during lung development (but absent in adult lung tissue). Our data showed not only that GDNF is overexpressed at the transcript level in squamous non-small-cell lung carcinoma, but also that the GDNF protein is present in early-stage lesions. Reactivation of the fetal lung expressed GDNF in early lesions and its amplification in CIS suggests an early role in tumorigenesis. These results highlight the value of examining the genomes of pre-invasive stages of cancer at tiling resolution.

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“…Studies of molecular cloning have characterized two genes that encode the type 1 and type 2 5α-reductase isoenzymes (13,14). The 5α-reductase isoenzyme predominant in the skin is type 1 (SDR5A1) (15), which has 60% homology with 5α-reductase type 2 (SDR5A2) that is characteristic of the prostate gland (14). An increase in 5α-reductase activity was demonstrated in genital and pubic skin fibroblasts from hirsute patients in comparison to the skin of normal women (8,16).…”

Section: Introductionmentioning

confidence: 99%

The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals

Oliveira

Lhullier

Brum

et al. 2003

Braz J Med Biol Res

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The aim of the present study was to determine the expression of the genes for type 1 (SDR5A1) and type 2 (SDR5A2) 5α-reductase isoenzymes in scalp hairs plucked from 33 hirsute patients (20 with polycystic ovary syndrome and 13 with idiopathic hirsutism) and compare it with that of 10 men and 15 normal women. SDR5A1 and SDR5A2 expression was estimated by RT-PCR using the gene of the ubiquitously expressed protein ß 2 -microglobulin as an internal control. The results are expressed as arbitrary units in relation to ß 2 -microglobulin absorbance (mean ± SEM). SDR5A2 expression was not detected in any hair samples analyzed in this study. No differences were found in SDR5A1 mRNA levels between men and normal women (0.78 ± 0.05 vs 0.74 ± 0.06, respectively). SDR5A1 gene expression in the cells of hair plucked from the scalp of normal women (0.85 ± 0.04) and of women with polycystic ovary syndrome (0.78 ± 0.05) and idiopathic hirsutism (0.80 ± 0.06) was also similar. These results indicate that SDR5A1 gene expression in the follicular keratinocytes from the vertex area of the scalp seems not to be related to the differences in hair growth observed between normal men and women and hirsute patients. Further studies are needed to investigate the expression of the 5α-reductase genes in other scalp follicular compartments such as dermal papillae, and also in hair follicles from other body sites, in order to elucidate the mechanism of androgen action on the hair growth process and related diseases.

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Identification and selective inhibition of an isozyme of steroid 5 alpha-reductase in human scalp.

Cited by 112 publications

References 31 publications

RETRACTED: Comparison of finasteride versus flutamide in the treatment of hirsutism

RETRACTED: Comparison of finasteride versus flutamide in the treatment of hirsutism

Chromosome 5p aberrations are early events in lung cancer: implication of glial cell line-derived neurotrophic factor in disease progression

The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals

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