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The purpose of the present study was to investigate how the PRL stimulatory agents affected uterine carcinogenesis and to clarify the effects of PRL on endometrial adenocarcinoma progression in rats. Ten\u2010week\u2010old female Donryu rats were treated once with <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2032\u2010nitro\u2010<jats:italic>N<\/jats:italic>\u2010nitrosoguanidine (20\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>), followed by treatment with sulpiride (200\u2009ppm) or EGME (1250\u2009ppm) from 11\u2009weeks of age to 12\u2009months of age. Sulpiride treatment inhibited the incidence of uterine adenocarcinoma and precancerous lesions of atypical endometrial hyperplasia, whereas EGME had no effect on uterine carcinogenesis. Sulpiride markedly prevented the onset of persistent estrus throughout the study period, and EGME delayed and inhibited the onset of persistent estrus. Moreover, sulpiride\u2010treated animals showed high PRL and P4 serum levels without changes in the levels of estradiol\u201017\u03b2, low uterine weights and histological luteal cell hypertrophy. EGME did not affect serum PRL and P4 levels. These results suggest that the prolonged low estradiol\u201017\u03b2 to P4 ratio accompanied by persistent estrous cycle abnormalities secondary to the luteal stimulatory effects of PRL may explain the inhibitory effects of sulpiride on uterine carcinogenesis in rats. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3206","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T18:13:01Z","timestamp":1436897581000},"page":"769-776","source":"Crossref","is-referenced-by-count":5,"title":["Effects of sulpiride and ethylene glycol monomethyl ether on endometrial carcinogenicity in Donryu rats"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-0408","authenticated-orcid":false,"given":"Yoshikazu","family":"Taketa","sequence":"first","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Setagaya\u2010ku Tokyo Japan"},{"name":"Tsukuba Drug Safety, Global Drug Safety, Biopharmaceutical Assessments Core Function Unit, Eisai Product Creation Systems Eisai Co., Ltd.  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