{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:50:33Z","timestamp":1790542233181,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":6409,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[1989,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Using a stathmokinetic in vivo metaphase\u2010arrest technique, we studied cell proliferation and histological changes in the ventral (VP) and dorsolateral (DLP) prostate lobes of intact Noble (Nb) rats following a 16 week treatment with testosterone (T) or 5\u03b1\u2010dihydrotestosterone (DHT) administered separately or in combination with various estrogens. The combined treatment of rats with T and either estradiol\u201017\u03b2, estradiol\u201017\u03b1, or moxestrol induced florid dysplasia and markedly elevated the mitotic index (MI) in affected regions of the DLP. In contrast, joint DHT and estrogen treatment caused only mild proliferative lesions in this lobe. The separate administration of either androgens or estrogens suppressed epithelial proliferation in both the VP and DLP, but they differed in their histological effects on these tissues. Thus DHT or T alone maintained the morphological integrity of VP and DLP, whereas E<jats:sub>2<\/jats:sub>\u201017\u03b2 or moxestrol caused massive atrophy of both lobes. Although dysplastic foci were randomly scattered throughout the DLP, the most dramatic lesions occurred in periurethral ducts. With the exception of joint T and E<jats:sub>2<\/jats:sub>\u201017\u03b1 treatment, which induced proliferative alterations in the VP, dysplasia was always restricted to the DLP of all animals receiving both androgens and estrogens. Concomitant comparative stathmokinetic studies of the prostates of T\u2010treated castrates suggest that protracted androgen\u2010supported estrogen stimulation of the DLP is necessary to overcome factors that normally limit cell proliferation.<\/jats:p>","DOI":"10.1002\/pros.2990150104","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T01:38:35Z","timestamp":1172021915000},"page":"23-40","source":"Crossref","is-referenced-by-count":116,"title":["Androgen\u2010supported estrogen\u2010enhanced epithelial proliferation in the prostates of intact noble rats"],"prefix":"10.1002","volume":"15","author":[{"given":"Irwin","family":"Leav","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick B.","family":"Merk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.\u2010L.","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuk\u2010Mei","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,20]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1951.tb00149.x"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(72)90005-6"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/BF02889356","article-title":"The cell proliferation of epithelial metaplasia in the prostate gland: An autographic in vitro study","volume":"19","author":"Helpap B","year":"1975","journal-title":"Virchows Arch Cell Pathol"},{"key":"e_1_2_1_5_2","first-page":"69","article-title":"Bipotentiality of response to sex hormones by the prostate of castrated or hypophysectomized dogs: direct effects of estrogen","volume":"93","author":"Leav I","year":"1978","journal-title":"Am J Pathol"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990110206"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)51020-4"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-57-1-166"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109757"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(82)91275-X"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(78)90116-4"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/80.13.1045"},{"key":"e_1_2_1_13_2","first-page":"113","article-title":"Prostate carcinoma of the Nb rat in relation to hormones","volume":"23","author":"Noble RL","year":"1982","journal-title":"Int Rev Exp Pathol"},{"key":"e_1_2_1_14_2","first-page":"255","article-title":"The induction of Nb rat prostatic carcinomas","volume":"4","author":"Drago JR","year":"1984","journal-title":"Anticancer Res"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(86)80156-3"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(08)60951-6"},{"key":"e_1_2_1_17_2","first-page":"1","article-title":"Control of proliferative growth in androgen responsive organs and neoplasm","volume":"2","author":"Bruchovsky N","year":"1976","journal-title":"Adv Sex Hormone Res"},{"key":"e_1_2_1_18_2","first-page":"131","volume-title":"Male Accessory Sex Glands","author":"Touhimaa P","year":"1980"},{"key":"e_1_2_1_19_2","first-page":"609","article-title":"Testosterone\u2010mediated increase in 5\u03b1\u2010dihydrotestosterone content, nuclear androgen receptor levels, and cell division in an androgen\u2010independent prostate carcinoma of Noble rats","volume":"48","author":"Ho S\u2010M","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_1_20_2","first-page":"643","article-title":"The metaphase arrest technique","volume":"13","author":"Wright NA","year":"1980","journal-title":"Cell Tissue Kinet"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990100108"},{"key":"e_1_2_1_22_2","first-page":"4909","article-title":"Perspectives on elonogenic tumor cells, stem cells, and oncogenes","volume":"44","author":"Buick RN","year":"1984","journal-title":"Cancer Res"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287397809529667"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091970202"},{"key":"e_1_2_1_25_2","first-page":"437","article-title":"Ultrastructural and biochemical expressions of divergent differentiation in prostates of castrated dogs treated with estrogen and androgen","volume":"47","author":"Merk FB","year":"1982","journal-title":"Lab Invest"},{"key":"e_1_2_1_26_2","first-page":"442","article-title":"Multiple phenotypes of prostatic glandular cells in castrated dogs after individual or combined treatment with androgen and estrogen. 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