Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components

Alessandro Pitruzzella, Daniela D'Amico, Francesco Cappello, Valentina Di Felice, Francesca Rappa, Rosario Barone, Antonella Marino Gammazza, Claudia Sangiorgi, Francesca Di Gaudio, Antonella Marino Gammazza, Stefania Schiavone, Gabriele Sani, Alessandro Pitruzzella, Nicola Locorotondo, Emanuela Turillazzi, Rosario Barone, Francesca Rappa, Monica Salerno, Fulvio Barone, Amos TamboFrancesca Di Gaudio, Luigi Cipolloni, Venerando Rapisarda, Francesco Cappello, Cristoforo Pomara, Valentina Di Felice

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13 Citations (Scopus)

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.
Original languageEnglish
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

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