TY - JOUR
T1 - Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components
AU - Cappello, Francesco
AU - Di Felice, Valentina
AU - Barone, Rosario
AU - Di Gaudio, Francesca
AU - D'Amico, Daniela
AU - Sangiorgi, Claudia
AU - Marino Gammazza, Antonella
AU - Rappa, Francesca
AU - Pitruzzella, Alessandro
AU - Marino Gammazza, Antonella
AU - Schiavone, Stefania
AU - Sani, Gabriele
AU - Pitruzzella, Alessandro
AU - Locorotondo, Nicola
AU - Di Gaudio, Francesca
AU - Turillazzi, Emanuela
AU - Barone, Rosario
AU - Rappa, Francesca
AU - Salerno, Monica
AU - Barone, Fulvio
AU - Tambo, Amos
AU - Di Gaudio, Francesca
AU - Cipolloni, Luigi
AU - Rapisarda, Venerando
AU - Cappello, Francesco
AU - Pomara, Cristoforo
AU - Di Felice, Valentina
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Blood-testis barrier
KW - Cell Biology
KW - MMP-2
KW - MMP-9
KW - MUC1
KW - Molecular Medicine
KW - Nandrolone decanoate
KW - TJP1
KW - Testosterone
KW - Blood-testis barrier
KW - Cell Biology
KW - MMP-2
KW - MMP-9
KW - MUC1
KW - Molecular Medicine
KW - Nandrolone decanoate
KW - TJP1
KW - Testosterone
UR - http://hdl.handle.net/10447/225171
UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1582-4934
M3 - Article
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
ER -