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Despite its efficacy for treating androgenetic alopecia, finasteride, an inhibitor of 5α‐reductase (i.e., the enzyme converting testosterone, T, into dihydrotestosterone, DHT), is associated with several side effects including sexual dysfunction (e.g., erectile dysfunction). These side effects may persist after drug suspension, inducing the so‐called post‐finasteride syndrome (PFS). The effects of subchronic treatment with finasteride (i.e., 20 days) and its withdrawal (i.e., 1 month) in rat corpus cavernosum have been explored here. Data obtained show that the treatment was able to decrease the levels of the enzyme 5α‐reductase type II in the rat corpus cavernosum with increased T and decreased DHT levels. This local change in T metabolism was linked to mechanisms associated with erectile dysfunction. Indeed, by targeted metabolomics, we reported a decrease in the nitric oxide synthase (NOS) activity, measured by the citrulline/arginine ratio and confirmed by the decrease in NO2 levels, and a decrease in ornithine transcarbamylase (OTC) activity, measured by citrulline/ornithine ratio. Interestingly, the T levels are negatively correlated with NOS activity, while those of DHT are positively correlated with OTC activity. Finasteride treatment also induced alterations in the levels of other molecules involved in the control of penile erection, such as norepinephrine and its metabolite, epinephrine. Indeed, plasma levels of norepinephrine and epinephrine were significantly increased and decreased, respectively, suggesting an impairment of these mediators. Interestingly, these modifications were restored by suspension of the drug. Altogether, the results reported here indicate that finasteride treatment, but not its withdrawal, affects T metabolism in the rat corpus cavernosum, and this alteration was linked to mechanisms associated with erectile dysfunction. Data here reported could also suggest that the PFS sexual side effects are more related to dysfunction in a sexual central control rather than peripheral compromised condition. [ABSTRACT FROM AUTHOR]

Allopregnanolone, a 3α,5α‐progesterone metabolite, acts as a potent allosteric modulator of the γ‐aminobutyric acid type A receptor. In the present review, the synthesis of this neuroactive steroid occurring in the nervous system is discussed with respect to physiological and pathological conditions. In addition, its physiological and neuroprotective effects are also reported. Interestingly, the levels of this neuroactive steroid, as well as its effects, are sex‐dimorphic, suggesting a possible gender medicine based on this neuroactive steroid for neurological disorders. However, allopregnanolone presents low bioavailability and extensive hepatic metabolism, limiting its use as a drug. Therefore, synthetic analogues or a different therapeutic strategy able to increase allopregnanolone levels have been proposed to overcome any pharmacokinetic issues. [ABSTRACT FROM AUTHOR]

There are over 1000 varieties of steroids that have been reported in nature, including the endogenous sex steroid hormones (i.e., progesterone, testosterone, and 17β‐estradiol) and corticosteroids which are mainly synthesized by gonads and adrenals, respectively. In addition, an extra‐glandular steroidogenesis has been also reported in the brain and in the gastrointestinal tract (GIT). The reason why intestinal steroidogenesis and consequently gut steroids draw our attention is for the communication and interaction with the gut microbiota, which functions like a virtual endocrine organ, and it is also involved in the steroid production. Moreover, both GIT and gut microbiota communicate through neural, endocrine, and humoral ways with the brain, in the so‐called gut‐microbiota‐brain axis. On this basis, in this review, we will discuss several aspects such as (1) intestinal steroidogenesis and its possible regulation, (2) the potential role of gut steroids in physiopathological conditions, and (3) the role of microbiome in steroidogenesis and steroid metabolism. Overall, this review highlights new points of view considering steroid molecules as potential therapeutic approach for gastrointestinal disorders and brain comorbidities. [ABSTRACT FROM AUTHOR]