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We address the molecular events associated with hormonal castration by examining GnRH\u2010A effects on expression and phosphorylation of a number of key signaling proteins. Male beagles were treated for 5 months with a GnRH\u2010A implant, and then surgically castrated at 0, 3, 6, 12, and, 24 weeks after implant removal; untreated animals served as controls. GnRH\u2010A treatment led to activation of c\u2010Raf, Erk1\/2, and, p53 in the testes. Phosphorylation of p53 occurred at Ser15, consistent with activation of the c\u2010Raf\u2010Erk1\/2\u2010p53 signaling cascade that triggers growth arrest or apoptosis. GnRH\u2010A also suppressed the anti\u2010apoptotic protein Bcl\u2010xL; reduced phosphorylation of the transcription factors CREB and ATF1; and down\u2010regulated expression of StAR and P450scc, proteins involved in steroidogenesis. Although androgen receptor expression was little affected by GnRH\u2010A treatment, levels of ZIP9, a membrane\u2010bound Zn<jats:sup>2+<\/jats:sup> transporter that mediates non\u2010classical signaling of testosterone, were abrogated. All of these effects were reversed within 24 weeks after implant removal. Thus, molecular signatures of implant\u2010dependent hormonal castration include reversible cell cycle arrest and apoptosis, loss of steroidogenesis, and reduced transcriptional activity. <jats:italic>Mol. Reprod. Dev. 83: 1092\u20131101, 2016. \u00a9 2016 Wiley Periodicals, Inc<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrd.22751","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T16:26:42Z","timestamp":1476980802000},"page":"1092-1101","source":"Crossref","is-referenced-by-count":8,"title":["Signaling events associated with gonadotropin releasing hormone\u2010agonist\u2010induced hormonal castration and its reversal in canines"],"prefix":"10.1002","volume":"83","author":[{"given":"Ahmed","family":"Bulldan","sequence":"first","affiliation":[{"name":"Institute for Veterinary Physiology and Biochemistry Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazen","family":"Shihan","sequence":"additional","affiliation":[{"name":"Institute for Veterinary Physiology and Biochemistry Giessen 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