Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

Pomara, Cristoforo; Barone, Rosario; Gammazza, Antonella Marino; Sangiorgi, Claudia; Barone, Fulvio; Pitruzzella, Alessandro; Locorotondo, Nicola; Gaudio, Francesca Di; Salerno, Monica; Maglietta, Francesca; Sarni, Antonio Luciano; Felice, Valentina Di; Cappello, Francesco; Turillazzi, Emanuela

doi:10.1002/jcp.25272

Cited by 45 publications

(39 citation statements)

References 37 publications

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“…Furthermore, the expression of positive and negative regulators of cell proliferation such as Cyclin D1, Cyclin E, Cdk1/2 and p21, p53 resulted to be down-and up-regulated respectively, further confirming a strong repression of cell proliferation induced by nandrolone in HepG2 cells. An inhibitory effect on cell growth exerted by nandrolone has been already reported on other cell lines such as the Leydig cells 2,33 .…”

Section: Discussionmentioning

confidence: 60%

Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity

Agriesti

Tataranni

Pacelli

et al. 2020

Sci Rep

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nandrolone is a testosterone analogue with anabolic properties commonly abused worldwide, recently utilized also as therapeutic agent in chronic diseases, cancer included. Here we investigated the impact of nandrolone on the metabolic phenotype in HepG2 cell line. The results attained show that pharmacological dosage of nandrolone, slowing cell growth, repressed mitochondrial respiration, inhibited the respiratory chain complexes i and iii and enhanced mitochondrial reactive oxygen species (ROS) production. Intriguingly, nandrolone caused a significant increase of stemness-markers in both 2D and 3D cultures, which resulted to be CxIII-ROS dependent. Notably, nandrolone negatively affected differentiation both in healthy hematopoietic and mesenchymal stem cells. Finally, nandrolone administration in mice confirmed the up-regulation of stemness-markers in liver, spleen and kidney. Our observations show, for the first time, that chronic administration of nandrolone, favoring maintenance of stem cells in different tissues would represent a precondition that, in addition to multiple hits, might enhance risk of carcinogenesis raising warnings about its abuse and therapeutic utilization.

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Section: Discussionmentioning

confidence: 60%

Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity

Agriesti

Tataranni

Pacelli

et al. 2020

Sci Rep

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“…In a previous study, we demonstrated that ND treatment of Leydig cells interferes with the biosynthesis of testosterone in a dose increase-dependent fashion [13]. As a consequence of the results obtained in vitro, here an animal model was utilized to better understand the side effects of ND administration in sedentary and trained mice.…”

Section: Discussionmentioning

confidence: 91%

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

Barone

Pitruzzella

Gammazza

et al. 2017

J Cellular Molecular Medi

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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.

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“…As previously described, the equine estrogens are often contained in the HRT preparations: comparing the metabolites of equine estrogens with the human, a greater potential for causing oxidative damage was described (Zhang et al, 1999 ; Tibullo et al, 2013 ; Pomara et al, 2016 ). A metabolite of equine estrogen, 4-hydroxyequilenin, has been shown to cause oxidative damage and single-strand breaks in λ phage DNA (Chen et al, 1998 ) and in breast cancer cell lines, especially ER-positive cell lines (Liu et al, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

Role of Sex Hormones in the Control of Vegetative and Metabolic Functions of Middle-Aged Women

Monda¹,

Salerno

Moscatelli

et al. 2017

Front. Physiol.

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Aims: In women's life, menopause is characterized by significant physiological changes often associated with an increase in body mass and obesity-associated sicknesses. Numerous researches described interdependencies of estrogen deficiency, aging, and resting energy expenditure (REE) downfall in the obesity correlated with the menopause. The aim of this study was to determining whether healthy, obese menopausal women underwent HRT treatment, showed changes in their REE, autonomic asset, and assessment of oxidative stress in comparison with obese pre- and post-menopausal women.Methodology: In this study, we measured the body composition, the REE, the oxidative stress, the diet assimilation, and the autonomic nervous system activity in three groups: pre-menopause women (n = 50), post-menopause women following hormone-replacement therapy (HRT; n = 50), and post-menopause women not following HRT (n = 50).Results: In the group with HRT a significant increase of the sympathetic activity and REE was described. Finally this group showed a notable increment of oxidative stress compared with the others, and utilizing BIA instrument, the free fat mass was increased respect to the fat mass of obese women.Conclusion: The study highlights the importance of the HRT-related physiological changes that influence body weight in menopause women. This results are important because have a practical implications for prevention and/or treatment of the obesity.

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Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

Cited by 45 publications

References 37 publications

Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity

Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity

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

Role of Sex Hormones in the Control of Vegetative and Metabolic Functions of Middle-Aged Women

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