**6. Conclusions**

Orchidectomy alters different cell signalling pathways that are involved in vascular tone regulation. Orchidectomy increases: (i) the formation of superoxide anion and peroxynitrite; (ii) the activity of PKC; and (iii) the expression of COX-2, the production of prostanoids derived from COX-2, as well as their vasoconstrictor effect. These aspects seem to be physiologically relevant, since the balance between vasodilator/vasoconstrictor prostanoids is lost in favour of vasoconstrictor substances in arteries from orchidectomized rats. This situation could indicate a disadvantage in cardiovascular function in the absence of male sex hormones, thereby suggesting that testosterone has a beneficial influence on the vasculature. However, in the animals used in our study (6 months old) several compensatory mechanisms are working: reactive oxygen species are able to induce relaxation; PKC positively regulates nNOS and eNOS activity ensuring the maintenance of NO release; the activity and expression of SOD are increased in an attempt to compensate for the increased superoxide anion production. This intriguing information makes it essential to perform studies in vascular function taking into account different cell signalling pathways that are working simultaneously. Future studies in the research field of androgens on cell signaling pathways are needed, since they will be of important interest to implement therapeutic strategies that could improve vascular function.
