title: Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components.
abstract: The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography-mass spectrometry. Western blot analysis and quantitative real-time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression levels of the blood-testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein-1 (TJP1). ND stimulation deregulated metalloproteinase-9, metalloproteinase-2 (MMP-2) and the tissue inhibitor of MMP-2. Moreover, ND administration resulted in a mislocalization of mucin-1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP-2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone.
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Barone
authors.affiliation: Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.|Department of Neuroscience, Mental Health and Sense Organs (Nesmos), Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pitruzzella
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Marino Gammazza
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rappa
authors.affiliation: Department of Clinical and Experimental Medicine, Forensic Pathology, University of Foggia, Foggia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Salerno
authors.affiliation: Department of Clinical and Experimental Medicine, Forensic Pathology, University of Foggia, Foggia, Italy.|Department of Radiology, Scientific Institute Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Barone
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sangiorgi
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Amico
authors.affiliation: Locorotondo Labs srl, Palermo, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Locorotondo
authors.affiliation: Locorotondo Labs srl, Palermo, Italy.|Department of Pathobiology and Medical Biotechnology, University of Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Gaudio
authors.affiliation: Department of Forensic Pathology, Sapienza University of Rome, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cipolloni
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Felice
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Itlay.
authors.forename: Stefania
authors.initials: S
authors.lastname: Schiavone
authors.affiliation: Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Venerando
authors.initials: V
authors.lastname: Rapisarda
authors.affiliation: Department of Neuroscience, Mental Health and Sense Organs (Nesmos), Sapienza University of Rome, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sani
authors.affiliation: Department of Clinical and Experimental Medicine, Forensic Pathology, University of Foggia, Foggia, Italy.|Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Itlay.
authors.forename: Amos
authors.initials: A
authors.lastname: Tambo
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.affiliation: Department of Clinical and Experimental Medicine, Forensic Pathology, University of Foggia, Foggia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Turillazzi
authors.affiliation: Department of Clinical and Experimental Medicine, Forensic Pathology, University of Foggia, Foggia, Italy.|Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Itlay.|Department of Anatomy, University of Malta, Msida, Malta.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Pomara
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001814:Blood-Testis Barrier / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D010805:Physical Conditioning, Animal; D021381:Protein Transport / Q000187:drug effects; D057185:Sedentary Behavior; D015398:Signal Transduction; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D045930:Anabolic Agents; D018396:Mucin-1; D019714:Tissue Inhibitor of Metalloproteinases; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C577056:muc1 protein, mouse; D013739:Testosterone; D009277:Nandrolone; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D000077603:Nandrolone Decanoate
keywords: MMP-2; MMP-9; MUC1; TJP1; blood-testis barrier; nandrolone decanoate; testosterone