Endocrine Abstracts

Metabolic Syndrome (MetS) is a cluster of clinical conditions, associated to an increased cardiovascular and metabolic risk, to hypogonadism and erectile dysfunction (ED). Lifestyle modification (including physical exercise, PhyEx) and metformin (MET) are well-known treatments for the condition. We established an animal model of MetS that recapitulates the human phenotype, including andrologic derangements.

The aim of this study was to investigate in experimental MetS the effect of PhyEx or MET on penile erection and on hormonal and metabolic parameters.

Control (RD) and MetS rabbits were treated with MET (the last 18 days) or exercise-trained to run on a treadmill for 12 weeks. Penile tissue was collected for in vitro contractility study or gene expression.

MET, but not PhyEx, induced a reduction in visceral adiposity, blood pressure, triglycerides, glucose level and tolerance. MET increased testosterone (T), whereas PhyEx completely restored it. Ach-induced relaxation, hampered in MetS rabbits, was significantly ameliorated by MET and completely normalized by PhyEx. HFD determined a net reduction of electrical field (EF)-vasorelaxation in CC. The relaxant response to sildenafil, abolished in HFD rabbit CC, was restored by PhyEx. PhyEx normalized sodium nitroprusside (SNP)-induced relaxation, that was enhanced in MetS rabbits. Genes related to NO signaling were up-regulated by PhyEx, but not by MET. Similar results were obtained for smooth muscle-related genes. PDE5 expression was decreased in MetS rabbits and completely restored by PhyEx. Accordingly, sildenafil-induced increase in SNP relaxation was completely normalized by PhyEx.

In conclusion, PhyEx more than metformin, completely restored T levels and responsiveness to Ach and sildenafil in experimental MetS, even though it was less effective than metformin in reducing metabolic abnormalities. The effect of exercise training is most probably related to an improved NO signaling, including PDE5. Hence, PhyEx can be considered a new strategy to treat hypogonadism and ED related to MetS.