OBJEVTIVETo synthesize phenoxybutyric acid derivatives as 5α-reductase inhibitors and test their biological activities in vitro.

METHODSEight analogues as nonsteroidal 5α-reductase inhibitors were designed and synthesized by substitution reaction of 6-(4-phenyl-piperazine-1-yl)-3(2H)-pyridazinone with phenoxybutyric acid derivatives.

RESULTS AND CONCLUSIONThe structures of the compounds were characterized by 1H-NMR and MS. Biological evaluation indicated that 7 out of the 8 compounds exhibited moderate 5α-reductase inhibitory activities, especially the compounds A1 and A7 with inhibition rates reaching 12.50% and 19.64% at the concentration of 3.3 × 10⁻⁵ mol/L, respectively.

5-alpha Reductase Inhibitors ; chemical synthesis ; pharmacology ; Butyrates ; chemistry ; pharmacology ; Drug Design

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-β-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(trans-urticol-7-O-β-D-glucopyranoside, 7), cycloolivil-4-O-β-D-glucopyranoside(8), isolariciresinol-4'-O-β-D-glucopyranoside(9), and olivil-4'-O-β-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.
5-alpha Reductase Inhibitors ; Cholestenone 5 alpha-Reductase/pharmacology* ; Chromatography, High Pressure Liquid ; Lignans/pharmacology* ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Urticaceae/enzymology*

Humans ; Finasteride/pharmacology* ; Dutasteride/pharmacology* ; 5-alpha Reductase Inhibitors/pharmacology* ; Testosterone/metabolism* ; Hair Follicle/metabolism* ; Transcriptome ; Hair/metabolism*

AIMTo investigate the relationship between low androgen level and ultrastructure of vascular endothelium.

METHODSForty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5alpha-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed.

RESULTSSerum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P < 0.01); DHT concentrations of group D rats were significantly decreased (P < 0.01) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS.

CONCLUSIONThese results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.

5-alpha Reductase Inhibitors ; Animals ; Aorta ; drug effects ; ultrastructure ; Dihydrotestosterone ; blood ; Endothelium, Vascular ; drug effects ; ultrastructure ; Enzyme Inhibitors ; pharmacology ; Male ; Orchiectomy ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood ; pharmacology

BACKGROUND5&alpha;-Reductase inhibitors (5&alpha;-RI) act by inhibiting the conversion of testosterone to dihydrotestosterone (DHT), thereby preventing DHT induced benign prostatic hyperplasia. The existing 5&alpha;-RIs can be classified into two types: competitive and noncompetitive. Currently, limited evidence is available concerning the effect differences between the two types of 5&alpha;-RI on androgens. The purpose of this study was to assess the effects of competitive and noncompetitive 5&alpha;-RIs on serum and intra-prostatic androgens in beagle dogs.

METHODSTwenty beagles with spontaneous benign prostatic hyperplasia were randomly allocated into two groups: epristeride group (n = 10) in which beagles were treated with epristeride at 1 mg/kg once a day for 3 months, and finasteride group (n = 10) in which beagles were treated with finasteride at 1 mg/kg once a day for 3 months. The levels of intra-prostatic testosterone and DHT were measured before treatment and on day one after three months medication. Serum levels of testosterone and DHT were measured at the same time points. Changes in androgen levels before and after treatment were analyzed, and comparisons were made within each treatment group and between treatment groups.

RESULTSAfter 3-month treatment, serum and intra-prostatic DHT levels all decreased significantly in both the epristeride and finasteride groups. The change of DHT in serum was significantly higher in the finasteride group (-14% and -43% in epristeride and finasteride groups respectively, with P < 0.001); however there was no significant difference in the changes of intra-prostatic DHT between the two groups (-47% and -51% in epristeride and finasteride groups, respectively, P = 0.304). The decreases in DHT levels were accompanied by reciprocal increases in serum and intra-prostatic testosterone levels. Changes of testosterone were significantly higher in finasteride group both in serum (20% and 42% in epristeride and finasteride groups, respectively, P < 0.001) and in prostate tissue (18% and 29% in epristeride and finasteride groups, respectively, P = 0.004).

CONCLUSIONSTwo types of 5&alpha;-RI have similar effects in reducing DHT in prostate tissue in beagles. Competitive 5&alpha;-RI may reduce serum DHT to a greater scale, and significantly increase testosterone in beagle serum and prostate.

5-alpha Reductase Inhibitors ; pharmacology ; Androgens ; blood ; metabolism ; Androstadienes ; pharmacology ; Animals ; Dihydrotestosterone ; blood ; metabolism ; Dogs ; Finasteride ; pharmacology ; Male ; Prostate ; drug effects ; metabolism

OBJECTIVETo identify the role of 5alpha-reductase in the spermatogenesis of male rats by studying the effect of two 5alpha-reductase inhibitors, Epristeride and Finasteride, on the spermatogenesis in male Sprague-Dawley (SD) rats.

METHODSChanges in the weight of the testis, serum testosterone and dihydrotestosterone levels, epididymal sperm count, and reproductive function were observed and analyzed after the two 5alpha-reductase inhibitors were administered to male SD rats orally.

RESULTSThe experiment showed that in comparison with control animals, both the two 5alpha-reductase inhibitors: 1. suppressed the development of the prostate and reduced the weight of the testis in the experimental groups (P < 0.05); 2. decreased the serum level of dihydrotestosterone and enhanced testosterone; 3. inhibited epididymal sperm count and productive function.

CONCLUSIONHigh dosages of the 5alpha-reductase inhibitor, Epristeride, can suppress the development of the prostate and reduce the weight of the testis, decrease dihydrotestosterone, and inhibit spermatogenesis and productive function in male rats.

5-alpha Reductase Inhibitors ; Androstadienes ; pharmacology ; Animals ; Dose-Response Relationship, Drug ; Finasteride ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; drug effects

OBJECTIVETo investigate whether 5alpha-reductase inhibitor and dihydrotestosterone (DHT) play a role in spermatogenesis in male rats.

METHODSThirty-two male rats were divided into 4 groups (Groups C, T, F and FT). Group C received plant oil injection and oral starch perfusion, Group T testosterone undecanoate (TU, 20 mg/kg) injection and oral starch perfusion, Group F plant oil injection and oral Finasteride perfusion, and Group FT TU (20 mg/kg) injection and oral Finasteride perfusion. Data on serum T and DHT, sperm count, sperm mobility and reproductive function were collected and analysed.

RESULTS(1) 5alpha-reductase inhibitor, Finasteride and TU reduced the weight of the testis and epididymis in the experiment groups compared with the negative control (Group C), but TU increased the weight of the prostate while Finasteride decreased it compared with the positive control (Group T). TU combined with Finasteride could counteract the effect of the weight increase of the prostate, but not that of the testis. (2) Finasteride, or Finasteride combined with TU, reduced the DHT but increased the testosterone level in comparison with the control group. (3) Both Finasteride and TU could inhibit epididymal sperm count and reproductive function compared with the control, but the effect was less significant in Group FT than in Group F.

CONCLUSIONHigh dosages of 5alpha-reductase inhibitor, Finasteride, can suppress male reproductive function, but the inhibiting effect could be counteracted by administration of 5alpha-reductase inhibitor along with TU.

Animals ; Cholestenone 5 alpha-Reductase ; antagonists & inhibitors ; Dihydrotestosterone ; pharmacology ; Dose-Response Relationship, Drug ; Finasteride ; pharmacology ; Male ; Organ Size ; Prostate ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; drug effects ; Testis ; drug effects ; pathology ; Testosterone ; analogs & derivatives ; pharmacology