{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:41:24Z","timestamp":1792723284927,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,11]],"date-time":"2006-12-11T00:00:00Z","timestamp":1165795200000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Estrogens play a physiologic role during prostate development with regard to programming stromal cells and directing early morphogenic events. However, if estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate branching morphogenesis and cellular differentiation will result, a process referred to as neonatal imprinting or developmental estrogenization. These perturbations are associated with an increased incidence of prostatic lesions with aging, which include hyperplasia, inflammation, and dysplasia. To understand how early estrogenic exposures can permanently alter the prostate and predispose it to neoplasia, we examined the effects of estrogens on prostatic steroid receptors and key developmental genes. Transient and permanent alterations in prostatic AR, ER\u03b1, ER\u03b2, and RARs are observed. We propose that estrogen\u2010induced alterations in these critical transcription factors play a fundamental role in initiating prostatic growth and differentiation defects by shifting the prostate from an androgen\u2010dominated gland to one whose development is regulated by estrogens and retinoids. This in turn leads to specific disruptions in the expression patterns of key prostatic developmental genes that normally dictate morphogenesis and differentiation. Specifically, we find transient reductions in <jats:italic>Nkx<\/jats:italic>3.1 and permanent reductions in <jats:italic>Hox<\/jats:italic>b\u201013, which lead to differentiation defects particularly within the ventral lobe. Prolonged developmental expression of <jats:italic>Bmp<\/jats:italic>\u20104 contributes to hypomorphic growth throughout the prostatic complex. Reduced expression of <jats:italic>Fgf<\/jats:italic>10 and <jats:italic>Shh<\/jats:italic> and their cognate receptors in the dorsolateral lobes leads to branching defects in those specific regions in response to neonatal estrogens. We hypothesize that these molecular changes initiated early in life predispose the prostate to the neoplastic state upon aging.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1386.009","type":"journal-article","created":{"date-parts":[[2007,2,2]],"date-time":"2007-02-02T18:28:39Z","timestamp":1170440919000},"page":"1-13","source":"Crossref","is-referenced-by-count":108,"title":["The Role of Estrogens in Normal and Abnormal Development of the Prostate Gland"],"prefix":"10.1111","volume":"1089","author":[{"given":"GAIL S.","family":"PRINS","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LIWEI","family":"HUANG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LYNN","family":"BIRCH","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YONGBING","family":"PU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12,11]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990010202"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000600105"},{"key":"e_1_2_8_4_2","first-page":"17","volume-title":"Male Accessory Sex Glands","author":"Zondek L.H.","year":"1980"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10103"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(02)00575-1"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(85)90275-4"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod45.2.308"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990240204"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.130.6.3703"},{"key":"e_1_2_8_11_2","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1210\/endo.136.3.7867585","article-title":"The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen","volume":"136","author":"Prins G.S.","year":"1995","journal-title":"Endocrinology"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.132.6.2387"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0035"},{"key":"e_1_2_8_14_2","first-page":"247","volume-title":"Prostate: Basic and Clinical Aspects","author":"Prins G.S.","year":"1977"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0965-3_5"},{"key":"e_1_2_8_16_2","article-title":"Neonatal estrogen exposure alters epithelial differentiation in rat prostate through down regulation of Hoxb\u201013","volume":"25","author":"Pu Y.","year":"2004","journal-title":"J. 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