{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:36:10Z","timestamp":1779377770699,"version":"3.53.1"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,1]],"date-time":"2005-06-01T00:00:00Z","timestamp":1117584000000},"content-version":"vor","delay-in-days":5449,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1990,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of studies was conducted to determine the developmental toxicity of the 5\u03b1\u2010reductase inhibitor finasteride (MK\u20100906) in rats. This compound was administered orally once daily to pregnant rats during various extended treatment periods during gestation. F<jats:sub>1<\/jats:sub> offspring were evaluated on Day 20 of gestation as well as postnatally through mating to produce an F<jats:sub>2<\/jats:sub> generation. MK\u20100906 treatment induced dosage\u2010related incidences of hypospadias (penischisis) in male offspring with a threshold dosage level near 0.1 mg\/kg\/day and a 100% effect level of 100 mg\/kg\/day (with dosing through Day 20 of gestation). MK\u20100906 also caused decreased anogenital distance in male offspring. The dosage response for this effect (ranging from a 4.2% decrease at 0.003 mg\/kg\/day to a 38% decrease at 100 mg\/kg\/day) was more shallow than that for hypospadias. The decreases in anogenital distance were at least partially reversible postnatally with essentially complete recovery at dosages up to 0.1 mg\/kg\/day. There was also a dosage\u2010related, temporary induction of nipples in F<jats:sub>1<\/jats:sub> males. All of these effects were apparent following treatment on Days 6 through 17 of gestation but were more pronounced when dosing extended to Day 20 of gestation. Slight maternal toxicity consisting of minor decreases in body weight gain occurred only at dosages of 3 mg\/kg\/day and higher, indicating the selective nature of the developmental toxicity. The 5\u03b1\u2010reductase enzyme located in the rat fetal genital tubercle was studied in vitro and compared to that in the adult ventral prostate. The values for K<jats:sub>m<\/jats:sub>, V<jats:sub>max<\/jats:sub>, and IC<jats:sub>50<\/jats:sub> for inhibition by MK\u20100906 were similar in the two tissues, suggesting that the enzymatic proteins in the genital tubercle and ventral prostate may be similar.<\/jats:p>","DOI":"10.1002\/tera.1420420111","type":"journal-article","created":{"date-parts":[[2005,6,12]],"date-time":"2005-06-12T04:18:15Z","timestamp":1118549895000},"page":"91-100","source":"Crossref","is-referenced-by-count":106,"title":["External genitalia abnormalities in male rats exposed in utero to finasteride, a 5\u03b1\u2010reductase inhibitor"],"prefix":"10.1002","volume":"42","author":[{"given":"Robert L.","family":"Clark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Antonello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Grossman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. David","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Bagdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasa","family":"Prahalada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-89-1-16"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-169-41309"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-124-2-727"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-125-5-2434"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-122-3-1159"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0710289"},{"key":"e_1_2_1_8_1","unstructured":"Gormley G. R. Rittmaster H.Gregg K.Lasseter D.Ferguson andE.Stoner(1989) Dose response effect of an orally active 5\u2010alpha\u2010reductase inhibitor (MK\u20100906) in man.Endocrinology in press."},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(84)90383-2"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420120209"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-116-2-807"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-1-132"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(76)90175-3"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.2307\/2282717"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"7168","DOI":"10.1016\/S0021-9258(19)40924-1","article-title":"Diminished 5\u03b1\u2010reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, Type 2","volume":"250","author":"Moore R.","year":"1975","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_16_1","first-page":"466","volume-title":"In: Methods in Enzymology","author":"Moore R. J.","year":"1975"},{"key":"e_1_2_1_17_1","first-page":"209","article-title":"Autoradiographic studies of the localisation of androgen\u2010binding cells in the genital tubercles of fetal rats","volume":"151","author":"Murakami R.","year":"1987","journal-title":"J. Anat."},{"key":"e_1_2_1_18_1","first-page":"337","article-title":"Aspects of androgen\u2010dependent events as studied by antiandrogens","volume":"26","author":"Neumann F.","year":"1970","journal-title":"Recent Prog. Horm. Res."},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1970.0057"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00161a028"},{"key":"e_1_2_1_21_1","first-page":"402A","article-title":"Administration of MK\u2010 0906, a 4\u2010azasteroid compound results in marked suppression of serum dihydrotestosterone in healthy men","volume":"35","author":"Stoner E.","year":"1987","journal-title":"Clin. Res."},{"key":"e_1_2_1_22_1","first-page":"168","volume-title":"Endocrine Society Program and Abstracts Book","author":"Tenover J.","year":"1989"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.2307\/2530666"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7010602"}],"container-title":["Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftera.1420420111","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tera.1420420111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T10:01:51Z","timestamp":1697968911000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tera.1420420111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,7]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1990,7]]}},"alternative-id":["10.1002\/tera.1420420111"],"URL":"https:\/\/doi.org\/10.1002\/tera.1420420111","archive":["Portico"],"relation":{},"ISSN":["0040-3709","1096-9926"],"issn-type":[{"value":"0040-3709","type":"print"},{"value":"1096-9926","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,7]]}}}