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This study was designed to evaluate the effect of in vivo Doxa <jats:italic>po<\/jats:italic>\u2010application, in clinically relevant dose, on: (i) steroidogenic machinery homeostasis; (ii) <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> signalling; (iii) transcription profile of ADR in Leydig cells of adult rats. The results showed that <jats:italic>po<\/jats:italic>\u2010application of Doxa for once (1\u00d7Doxa), or for two (2\u00d7Doxa) or 10 (10\u00d7Doxa) consecutive days significantly disturbed steroidogenic machinery homeostasis in Leydig cells. Doxa <jats:italic>po<\/jats:italic>\u2010application significantly decreased circulating luteinizing hormone and androgens levels. The level of androgens in testicular interstitial fluid and that extracted from testes obtained from 1\u00d7Doxa\/2\u00d7Doxa rats decreased, although it remained unchanged in 10\u00d7Doxa rats. Similarly, the ex vivo basal androgen production followed in testes isolated from 1\u00d7Doxa\/2\u00d7Doxa rats decreased, while remained unchanged in 10\u00d7Doxa rats. Differently, ex vivo testosterone production and steroidogenic capacity of Leydig cells isolated from 1\u00d7Doxa\/2\u00d7Doxa rats was stimulated, while 10\u00d7Doxa had opposite effect. In the same cells, <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> content\/release showed similar stimulatory effect, but back to control level in Leydig cells of 10\u00d7Doxa. 1\u00d7Doxa\/2\u00d7Doxa decreased transcripts for <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> specific phosphodiesterases <jats:italic>Pde7b\/Pde8b,<\/jats:italic> whereas 10\u00d7Doxa increased <jats:italic>Pde4d<\/jats:italic>. All types of treatment reduced the expression of genes encoding protein kinase A (PRKA) regulatory subunit (<jats:italic>Prkar2b<\/jats:italic>), whereas only 10\u00d7Doxa stimulated catalytic subunit (<jats:italic>Prkaca)<\/jats:italic>. Doxa application more affected <jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> signalling: stimulated transcription of constitutive nitric oxide synthases (<jats:italic>Nos1, Nos3<\/jats:italic>) in time\u2010dependent manner, whereas reduced inducible <jats:italic>Nos2<\/jats:italic>. 10\u00d7Doxa increased guanylyl cyclase 1 transcript and PRKG1 protein in Leydig cells. Orally applied Doxa significantly disturbed the transcriptional \u2018signature\u2019 of steroidogenic machinery, <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content> signalling and ADRs and \u03b2\u2010ADRs kinases in Leydig cells, thus giving new molecular insights into the role of <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/adrenalin signalling in Leydig cells homeostasis.<\/jats:p>","DOI":"10.1111\/j.2047-2927.2012.00035.x","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T03:10:59Z","timestamp":1354245059000},"page":"332-347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, <scp>cAMP<\/scp>\/<scp>cGMP<\/scp> signalling and adrenergic receptors in Leydig cells of adult rats"],"prefix":"10.1111","volume":"1","author":[{"given":"N. 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