Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finasteride is a specific 5 alpha-reductase inhibitor that has been shown to reduce the size of human benign prostatic hyperplasia (BPH) by inhibiting the intraprostatic conversion of testosterone to 5 alpha-dihydrotestosterone. The aim of the present in vitro study was to describe in more detail the inhibitory effect of finasteride on 5 alpha-reductase in epithelium and stroma of human BPH. 5 alpha-Reductase activity in epithelium and stroma was inhibited dose-dependently by finasteride. The mean IC50 (50% inhibitory concentration) values, determined in the presence of various testosterone concentrations, were generally 2- to 4-fold lower in epithelium than in stroma. With finasteride concentrations greater than 5 nM, competitive inhibition of 5 alpha-reductase occurred both in epithelium and stroma. The mean inhibition constant Ki[nM +/- SEM] was 7 +/- 3 and 31 +/- 3 in epithelium and stroma, respectively. In the presence of finasteride concentrations < or = 5 nM, the epithelial 5 alpha-reductase seems to be inhibited in an uncompetitive manner, whereas such low finasteride concentrations cause either no inhibition (1-2 nM) or competitive inhibition (5 nM) in stroma. Our present study provides evidence that the inhibitory effect of finasteride on 5 alpha-reductase is much stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.
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PMID:5 alpha-reductase inhibition by finasteride (Proscar) in epithelium and stroma of human benign prostatic hyperplasia. 753 80

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.
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PMID:Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin. 763 2

The effects of the 5 alpha-reductase inhibitor, finasteride, on scalp skin testosterone (T) and dihydrotestosterone (DHT) levels were studied in patients with male pattern baldness. In a double blind study, male patients undergoing hair transplantation were treated with oral finasteride (5 mg/day) or placebo for 28 days. Scalp skin biopsies were obtained before and after treatment for measurement of T and DHT by high pressure liquid chromatography-RIA. In 10 male subjects studied at baseline, mean (+/- SEM) DHT levels were significantly higher in bald (7.37 +/- 1.24 pmol/g) compared to hair-containing (4.20 +/- 0.65 pmol/g) scalp, whereas there was no difference in mean T levels at baseline. In bald scalp from 8 patients treated with finasteride, the mean DHT concentration decreased from 6.40 +/- 1.07 pmol/g at baseline to 3.62 +/- 0.38 pmol/g on day 28. Scalp T levels increased in 6 of 8 subjects treated with finasteride. Finasteride decreased the mean serum DHT concentration from 1.36 +/- 0.18 nmol/L (n = 8) at baseline to 0.46 +/- 0.10 nmol/L on day 28 and had no effect on serum T. There were no significant changes in scalp or serum T or DHT in placebo-treated patients. In this study, male subjects treated with 5 mg/day finasteride for 4 weeks had significantly decreased concentrations of DHT in bald scalp, resulting in a mean level similar to the baseline levels found in hair-containing scalp.
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PMID:The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. 807 49

Finasteride, a 5 alpha-reductase inhibitor, decreases prostate size and improves symptoms in men with benign prostatic hyperplasia. However, little is known about prostate histopathology in men taking finasteride. To determine the mechanism by which finasteride reduces prostate size, tissue was collected at the time of prostatectomy from men taking either no medication (n = 10) or 5 mg finasteride daily for 6-18 days (n = 6; group 1), 23-73 days (n = 5; group 2), or 3 months to 4 yr (n = 5; group 3). To assess whether finasteride causes epithelial atrophy, morphometric measurement of epithelial cell and duct width was used. The mean epithelial cell width in control prostates (mean +/- SEM, 21 +/- 0.7 microns) decreased with duration of treatment to 19 +/- 1 microns in group 1, 15 +/- 2 microns in group 2, and 8 +/- 0.3 microns in group 3. Mean duct width decreased from 135 +/- 6 microns in the control prostates to 128 +/- 10 microns in group 1, 103 +/- 3 microns in group 2, and 63 +/- 6 microns in group 3. To assess whether prostate cell death was occurring, sections were in situ end labeled for DNA breaks and immunostained for tissue transglutaminase (tTG), a marker of apoptosis (programmed cell death). The percentage of epithelial cells staining for DNA breaks was 0.4 +/- 0.2 in control prostates, 2.8 +/- 0.9 in group 1, 1.7 +/- 0.5 in group 2, and 0.7 +/- 0.3 microns in group 3. Anti-tTG staining of epithelial cells was graded on a scale of 0-4. In control prostates, 3 +/- 1% of the ducts were grade 3 or 4 (> 50% of epithelial cells staining). In finasteride-treated prostates, 2 +/- 2% of the prostates in group 1, 13 +/- 4% of the prostates in group 2, and 0.5 +/- 0.5% of the prostates in group 3 were grade 3-4. These results indicate that a progressive decrease in epithelial cell size and function occurs during the first several months in the prostates of men treated with finasteride. The staining for DNA breaks and the tTG staining also indicate that an increased rate of apoptosis is occurring transiently in these prostates. We conclude that finasteride causes prostate involution through a combination of atrophy and cell death.
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PMID:Evidence for atrophy and apoptosis in the prostates of men given finasteride. 863 9

Finasteride is a well known steroid 5alpha-reductase inhibitor. In this context, recently we have shown that in human benign prostatic hyperplasia (BPH) finasteride inhibits the 5alpha-reduction of testosterone to dihydrostestosterone (DHT) more effectively in the epithelium as compared to the stroma. The aim of the present study was to describe in epithelium and stroma of human BPH the effect of finasteride on the 5alpha-reduction of androstenedione, that is the second main circulating androgen in men, to androstanedione. Using a finasteride concentration of 75 nM and an androstenedione concentration of 220 nM, the mean inhibition [% +/- SEM] of 5alpha-reductase activity was significantly higher in epithelium (69 +/- 2) than in stroma (52 +/- 4). Both in epithelium and stroma, this inhibition of 5alpha-reductase activity was dose-dependent and competitive. Dixon plots as well as slope replots of Lineweaver-Burk plots showed that the mean inhibition constant Ki (nM +/- SEM) was significantly lower in epithelium (10 +/- 1 and 11 +/- 2, respectively) than in stroma (33 +/- 7 and 28 +/- 4, respectively) indicating a significantly stronger inhibitory effect of finasteride in epithelium. From those mean Ki values, it follows that in human BPH finasteride inhibits equally well both the 5alpha-reduction of androstenedione to androstanedione and testosterone to DHT. Based on these inhibition studies, there is no evidence for the coexistence of substrate-specific 5alpha-reductases converting either testosterone or androstenedione. However, the striking difference in finasteride sensitivity of the 5alpha-reduction between epithelium and stroma could be due to a cell-type specific expression of structurally different 5alpha-reductases as well as to a different access of finasteride to 5alpha-reductase in epithelium and stroma where, compared to each other, the lipid environment is significantly different.
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PMID:In vitro inhibition of androstenedione 5alpha-reduction by finasteride in epithelium and stroma of human benign prostatic hyperplasia. 978 29