andrologyjournal.org/cgi/con … l/29/5/524
Abstract
Although gonadal and adrenal steroids heavily impact sexual function at the level of the brain, the nervous system also produces its own steroids de novo that may regulate sexual behavior and reproduction. Current evidence points to important roles for neurosteroids in sexual and gender-typical behaviors, control of ovulation, and behaviors that strongly influence sexual interest and motivation like aggression, anxiety and depression. At the cellular level, neurosteroids act through stimulating rapid changes in excitability and direct activation of membrane receptors in neurons. Thus, unlike peripheral steroids, neurosteroids can have immediate and specific effects on select neuronal pathways to regulate sexual function.
An alternative approach is to use drugs that specifically increase neurosteroid concentrations. The antipsychotic agents clozapine and olanzapine may improve schizophrenia by increasing brain allopregnanolone synthesis (Marx et al, 2006). Similarly, the reduction in aggression induced by fluoxetine may be directly caused by increased allopregnanolone levels in the CNS, because the drug is effective at levels 10-fold lower than those that block serotonin reuptake (Pinna et al, 2003). Negative side effects of drugs may also be explained by neurosteroid modulation. Notably, preliminary studies indicate that, as in the rodent, finasteride may increase depression in men as a result of the loss of allopregnanolone (eg, Altomare et al, 2002; Rahimi-Ardabili et al, 2006). This raises the possibility that lowered levels of the neurosteroid contribute to the reduced sexual desire reported for some patients. Treatment strategies that take into account effects on neurosteroids and the development of drugs that singularly target neurosteroid biosynthesis may therefore provide superior therapies for patients.
