Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia
The effects of the new steroidal antiandrogen TZP‐4238 on hormone‐induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One‐ to 2‐year‐old beagle dogs were castrated and administered 75 mg/week of andr...
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| Veröffentlicht in: | The Prostate 1992, Vol.21 (4), p.315-329 |
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| creator | Takezawa, Yutaka Fukabori, Yoshitatsu Yamanaka, Hidetoshi Mieda, Mamoru Honma, Seijiro Kushitani, Masanori Hamataki, Nobuyuki |
| description | The effects of the new steroidal antiandrogen TZP‐4238 on hormone‐induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One‐ to 2‐year‐old beagle dogs were castrated and administered 75 mg/week of androstanediol (A‐diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP‐4238, 0.1 mg/kg/day of TZP‐4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A‐diol plus E2. Treatment with 0.5 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP‐4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/ kg/day of TZP‐4238 decreased 5α‐reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP‐4238 and CMA were effective in inhibiting the growth of hormone‐induced canine BPH, and TZP‐4238 was at least 5 times more potent than CMA. TZP‐4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen‐AR complex. TZP‐4238 decreased 5α‐reductase activity by prevention of the androgen action described above. |
| doi_str_mv | 10.1002/pros.2990210408 |
| format | Article |
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One‐ to 2‐year‐old beagle dogs were castrated and administered 75 mg/week of androstanediol (A‐diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP‐4238, 0.1 mg/kg/day of TZP‐4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A‐diol plus E2. Treatment with 0.5 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP‐4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/ kg/day of TZP‐4238 decreased 5α‐reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP‐4238 and CMA were effective in inhibiting the growth of hormone‐induced canine BPH, and TZP‐4238 was at least 5 times more potent than CMA. TZP‐4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen‐AR complex. TZP‐4238 decreased 5α‐reductase activity by prevention of the androgen action described above.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.2990210408</identifier><identifier>PMID: 1281324</identifier><identifier>CODEN: PRSTDS</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Androstane-3,17-diol - analysis ; Animals ; antiandrogen ; Antineoplastic agents ; Biological and medical sciences ; canine BPH ; Chemotherapy ; Chlormadinone Acetate - analogs & derivatives ; Chlormadinone Acetate - pharmacology ; Cholestenone 5 alpha-Reductase ; Dihydrotestosterone - analysis ; Dogs ; Male ; Medical sciences ; Organ Size ; Oxidoreductases - analysis ; Pharmacology. Drug treatments ; Prostate - chemistry ; Prostate - pathology ; Prostatic Hyperplasia - diagnostic imaging ; Prostatic Hyperplasia - drug therapy ; Prostatic Hyperplasia - pathology ; Receptors, Androgen - analysis ; transrectal ultrasonography ; TZP-4238 ; Ultrasonography</subject><ispartof>The Prostate, 1992, Vol.21 (4), p.315-329</ispartof><rights>Copyright © 1992 Wiley‐Liss, Inc., A Wiley Company</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5018-aa7e88e38a5ce30b859faec90eab1346998b56133249c3415c00a4088bf3a7c33</citedby><cites>FETCH-LOGICAL-c5018-aa7e88e38a5ce30b859faec90eab1346998b56133249c3415c00a4088bf3a7c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.2990210408$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.2990210408$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,4024,27923,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4509904$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1281324$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takezawa, Yutaka</creatorcontrib><creatorcontrib>Fukabori, Yoshitatsu</creatorcontrib><creatorcontrib>Yamanaka, Hidetoshi</creatorcontrib><creatorcontrib>Mieda, Mamoru</creatorcontrib><creatorcontrib>Honma, Seijiro</creatorcontrib><creatorcontrib>Kushitani, Masanori</creatorcontrib><creatorcontrib>Hamataki, Nobuyuki</creatorcontrib><title>Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>The effects of the new steroidal antiandrogen TZP‐4238 on hormone‐induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One‐ to 2‐year‐old beagle dogs were castrated and administered 75 mg/week of androstanediol (A‐diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP‐4238, 0.1 mg/kg/day of TZP‐4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A‐diol plus E2. Treatment with 0.5 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP‐4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/ kg/day of TZP‐4238 decreased 5α‐reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP‐4238 and CMA were effective in inhibiting the growth of hormone‐induced canine BPH, and TZP‐4238 was at least 5 times more potent than CMA. TZP‐4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen‐AR complex. TZP‐4238 decreased 5α‐reductase activity by prevention of the androgen action described above.</description><subject>Androstane-3,17-diol - analysis</subject><subject>Animals</subject><subject>antiandrogen</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>canine BPH</subject><subject>Chemotherapy</subject><subject>Chlormadinone Acetate - analogs & derivatives</subject><subject>Chlormadinone Acetate - pharmacology</subject><subject>Cholestenone 5 alpha-Reductase</subject><subject>Dihydrotestosterone - analysis</subject><subject>Dogs</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Organ Size</subject><subject>Oxidoreductases - analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Prostate - chemistry</subject><subject>Prostate - pathology</subject><subject>Prostatic Hyperplasia - diagnostic imaging</subject><subject>Prostatic Hyperplasia - drug therapy</subject><subject>Prostatic Hyperplasia - pathology</subject><subject>Receptors, Androgen - analysis</subject><subject>transrectal ultrasonography</subject><subject>TZP-4238</subject><subject>Ultrasonography</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS1EVZbCmROSD4hb2nEcrx1xQquyRapoVYoq9WJNnAlryDqLnVXZf49XWbXqiZMP873nN28YeyfgVACUZ5s4pNOyrqEUUIF5wWYCal0AVOolm0GpoaiE1K_Y65R-AWQNlMfsWJRGyLKasea868iNiQ8dH1fEAz3wNFIcfIs9xzB6DG0cflLgt_fXRVVKw4fAV0NcD4EKH9qto5Y7DD4Q36cZcfSOr3Ybipsek8c37KjDPtHbw3vCfnw5v11cFJdXy6-Lz5eFUyBMgajJGJIGlSMJjVF1h-RqIGyErOZ1bRo1FzLHrp2shHIAmFc2TSdROylP2MfJN6f4s6U02rVPjvoeAw3bZLWUxoDQGTybQJfjpkid3US_xrizAuy-Vbvfwz61mhXvD9bbZk3tEz_VmOcfDnNMDvsuYnA-PWKVguy1xz5N2IPvafe_X-31zdX3ZyGKSe3zgf4-qjH-tnMttbJ335Z2qYy6uVgurJL_AOZmoDg</recordid><startdate>1992</startdate><enddate>1992</enddate><creator>Takezawa, Yutaka</creator><creator>Fukabori, Yoshitatsu</creator><creator>Yamanaka, Hidetoshi</creator><creator>Mieda, Mamoru</creator><creator>Honma, Seijiro</creator><creator>Kushitani, Masanori</creator><creator>Hamataki, Nobuyuki</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>1992</creationdate><title>Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia</title><author>Takezawa, Yutaka ; Fukabori, Yoshitatsu ; Yamanaka, Hidetoshi ; Mieda, Mamoru ; Honma, Seijiro ; Kushitani, Masanori ; Hamataki, Nobuyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5018-aa7e88e38a5ce30b859faec90eab1346998b56133249c3415c00a4088bf3a7c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Androstane-3,17-diol - analysis</topic><topic>Animals</topic><topic>antiandrogen</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>canine BPH</topic><topic>Chemotherapy</topic><topic>Chlormadinone Acetate - analogs & derivatives</topic><topic>Chlormadinone Acetate - pharmacology</topic><topic>Cholestenone 5 alpha-Reductase</topic><topic>Dihydrotestosterone - analysis</topic><topic>Dogs</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Organ Size</topic><topic>Oxidoreductases - analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Prostate - chemistry</topic><topic>Prostate - pathology</topic><topic>Prostatic Hyperplasia - diagnostic imaging</topic><topic>Prostatic Hyperplasia - drug therapy</topic><topic>Prostatic Hyperplasia - pathology</topic><topic>Receptors, Androgen - analysis</topic><topic>transrectal ultrasonography</topic><topic>TZP-4238</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takezawa, Yutaka</creatorcontrib><creatorcontrib>Fukabori, Yoshitatsu</creatorcontrib><creatorcontrib>Yamanaka, Hidetoshi</creatorcontrib><creatorcontrib>Mieda, Mamoru</creatorcontrib><creatorcontrib>Honma, Seijiro</creatorcontrib><creatorcontrib>Kushitani, Masanori</creatorcontrib><creatorcontrib>Hamataki, Nobuyuki</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takezawa, Yutaka</au><au>Fukabori, Yoshitatsu</au><au>Yamanaka, Hidetoshi</au><au>Mieda, Mamoru</au><au>Honma, Seijiro</au><au>Kushitani, Masanori</au><au>Hamataki, Nobuyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>1992</date><risdate>1992</risdate><volume>21</volume><issue>4</issue><spage>315</spage><epage>329</epage><pages>315-329</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><coden>PRSTDS</coden><abstract>The effects of the new steroidal antiandrogen TZP‐4238 on hormone‐induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One‐ to 2‐year‐old beagle dogs were castrated and administered 75 mg/week of androstanediol (A‐diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP‐4238, 0.1 mg/kg/day of TZP‐4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A‐diol plus E2. Treatment with 0.5 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP‐4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/ kg/day of TZP‐4238 decreased 5α‐reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP‐4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP‐4238 and CMA were effective in inhibiting the growth of hormone‐induced canine BPH, and TZP‐4238 was at least 5 times more potent than CMA. TZP‐4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen‐AR complex. TZP‐4238 decreased 5α‐reductase activity by prevention of the androgen action described above.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>1281324</pmid><doi>10.1002/pros.2990210408</doi><tpages>15</tpages></addata></record> |
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| ispartof | The Prostate, 1992, Vol.21 (4), p.315-329 |
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| subjects | Androstane-3,17-diol - analysis Animals antiandrogen Antineoplastic agents Biological and medical sciences canine BPH Chemotherapy Chlormadinone Acetate - analogs & derivatives Chlormadinone Acetate - pharmacology Cholestenone 5 alpha-Reductase Dihydrotestosterone - analysis Dogs Male Medical sciences Organ Size Oxidoreductases - analysis Pharmacology. Drug treatments Prostate - chemistry Prostate - pathology Prostatic Hyperplasia - diagnostic imaging Prostatic Hyperplasia - drug therapy Prostatic Hyperplasia - pathology Receptors, Androgen - analysis transrectal ultrasonography TZP-4238 Ultrasonography |
| title | Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia |
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