title: In vivo administration of doxazosin in rats highly decreases serum circulating levels of testosterone through a mechanism involving the testicular renin-angiotensin system.
abstract: Men are at greater risk of cardiovascular and renal diseases than women. Several hypertensive rat models also exhibit gender differences in blood pressure. Although the mechanisms responsible for these gender differences are not clear, androgens have been shown to promote hypertension. Testosterone is produced by Leydig cells under the regulation of catecholamines acting through both alpha- and beta-adrenoceptors. Some investigators have postulated a putative role of angiotensin II (Ang II) in modulating the action of gonadotropin in Leydig cells, inhibiting testosterone production. In the present work, we analysed the potential mechanism by which the testicular renin-angiotensin system (RAS) decreases the serum circulating levels of testosterone after the in vivo administration of the long-acting selective alpha(1)-adrenergic receptor antagonist doxazosin. RAS was analysed through assessment of the activity of its proteolytic regulatory enzymes. We can conclude that the testicular testosterone production, at least in rat, is regulated by catecholamines through a mechanism involving alpha(1)-adrenergic receptors and RAS, with a putative role for Ang III. Because doxazosin is usually used as a pharmacological therapy in the treatment of hypertension and benign prostatic hyperplasia, our results could also indicate that its benefits are due, at least in part, to decreased serum circulating levels of testosterone.
authors.affiliation: Experimental and Clinical Physiopathology Research Group, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, Jaén, Spain.
authors.forename: S
authors.initials: S
authors.lastname: de la Chica-Rodríguez
authors.forename: P
authors.initials: P
authors.lastname: Cortés-Denia
authors.forename: M J
authors.initials: MJ
authors.lastname: Ramírez-Expósito
authors.forename: J M Arias
authors.initials: JM
authors.lastname: de Saavedra
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Agesta
authors.forename: M del Cármen
authors.initials: Mdel C
authors.lastname: Pérez
authors.forename: J M
authors.initials: JM
authors.lastname: Martínez-Martos
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D018826:CD13 Antigens / Q000378:metabolism; D015536:Down-Regulation; D017292:Doxazosin / Q000008:administration & dosage*; D043384:Glutamyl Aminopeptidase / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013739:Testosterone / Q000097:blood*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D018340:Receptors, Adrenergic, alpha-1; D013739:Testosterone; D000626:Aminopeptidases; D018826:CD13 Antigens; C019721:aminopeptidase B; D043384:Glutamyl Aminopeptidase; D017292:Doxazosin