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

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.

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells.

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real-time PCR. The results obtained show that testosterone levels increase at a 3.9 µM concentration of nandrolone and return to the basal level a 15.6 µM dose of nandrolone. Nandrolone-induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a-hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down-regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects.

Progression of atherosclerotic lesions in the arteries and related gene expression: protective effect of phytonutrients.

We investigated the effect of the phytocompound Denshici-to-Chiusei (DTS) on the atherogenesis in apolipoprotein E(-/-)/low-density lipoprotein receptor(-/-) (apoE(-/-)/LDL receptor(-/-)) mice (E0). E0 mice were fed for 16 weeks with: (1) placebo or (2) 25 mg or (3) 50 mg of DTS/day. Aortic lesions were reduced by 38% (p < 0.01) in mice fed 50 mg/day, whereas peritoneal macrophages after both dosages had a 45%-60% lower (p < 0.01) capacity to oxidize LDL and to degrade it. This was associated with reduced LDL-associated lipoperoxides and a 22% inhibition (p < 0.05) in LDL aggregation. Tumor necrosis factor-alpha (TNF-alpha) expression and immunoreactivity in the aortic media increased five-fold, but this was significantly mitigated by DTS (50 mg > 25 mg) (p < 0.05). DTS significantly attenuated inflammatory mechanisms preceding atherogenesis with reduced LDL susceptibility to oxidation-aggregation.

Regulating redox balance gene expression in healthy individuals by nutraceuticals: a pilot study.

We tested the effect of a fermented papaya preparation (FPP; ORI, Gifu, Japan) on redox balance gene expression in 11 healthy nonsmoker, teetotaller individuals subjected to a detailed dietary and lifestyle questionnaire who refrained from any multivitamin supplement or fortified food. Redox status was assessed by erythrocyte and plasma parameters together with related leukocyte mRNA (glutathione peroxidase [GPx], superoxide dismutase [SOD], catalase, 8-oxoguanine glycosylase [hOGG1]) before/after 6 grams of FPP supplementation. At 2 and 4 weeks after FPP administration, plasma parameters remained unchanged, whereas FPP significantly upregulated all tested gene expression (p < 0.05). Although posttranscriptional/translation protein modifications do occur and larger and longer studies are awaited, these preliminary data suggest that a transcriptomic modification of key redox and DNA repair genes may offer further insights when attempting to interrelate "nutragenomics" to clinical phenomena.