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This study aimed to examine the effect of a potent progestin, (<jats:styled-content style=\"fixed-case\">LNG<\/jats:styled-content>), alone or in combination with testosterone (T) on spermatogenesis in adult rats, and to evaluate the functional role of the progesterone receptors (<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>s) in the testis. In comparison with a low dose of <jats:styled-content style=\"fixed-case\">LNG<\/jats:styled-content> treatment in adult rats for 4\u00a0weeks, T and T\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">LNG<\/jats:styled-content> treatment decreased testicular sperm count to 64.1 and 40.2% of control levels respectively. <jats:styled-content style=\"fixed-case\">LNG<\/jats:styled-content> induced germ cell apoptosis at stages I\u2013<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">XII<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">XIV<\/jats:styled-content>; T increased apoptosis at stages <jats:styled-content style=\"fixed-case\">VII<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">VIII<\/jats:styled-content>;<jats:styled-content style=\"fixed-case\"> LNG<\/jats:styled-content>\u00a0+\u00a0T treatment induced greater germ cell apoptosis at a wider range of seminiferous epithelial stages. <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and Western Blots showed that <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> was present in testes and up\u2010regulated during suppression of spermatogenesis induced by testicular hormonal deprivation. <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> knockout (<jats:styled-content style=\"fixed-case\">PRKO<\/jats:styled-content>) mice had larger testes, greater sperm production, increased numbers of Sertoli and Leydig cells. Suppression of gonadotropin and intratesticular T by Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content>\u2010antagonist treatment induced <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> promoter driven LacZ expression in Leydig cells of <jats:styled-content style=\"fixed-case\">PRKO<\/jats:styled-content> mice. This suggests that Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content>\u2010antagonist treatment while inducing germ cell apoptosis also up\u2010regulates <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>. We conclude that (i) <jats:styled-content style=\"fixed-case\">LNG<\/jats:styled-content>\u00a0+\u00a0T induced greater suppression of spermatogenesis through increase in germ cell apoptosis involving a wider range of seminiferous epithelial stages than either treatment alone, (ii) up\u2010regulation of <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> was associated with inhibition of spermatogenesis, (iii) <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> knockout mice showed increased sperm production suggesting that testicular <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> activated events play a physiological and pharmacological inhibitory role in the testis. These data support the hypothesis that in addition to its known suppressive effects on gonadotropins, progestins may have direct inhibitory actions on the testis.<\/jats:p>","DOI":"10.1111\/j.2047-2927.2012.00047.x","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T07:41:55Z","timestamp":1360827715000},"page":"308-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents"],"prefix":"10.1111","volume":"1","author":[{"given":"Yanhe","family":"Lue","sequence":"first","affiliation":[{"name":"Division of Endocrinology Department of Medicine Harbor\u2010UCLA Medical Center and Los Angeles Biomedical Research Institute Torrance CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of 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