Finasteride inhibits the disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis.
ABSTRACT Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively susceptible to recurrent, unprovoked seizures due to precipitating risk factors. Progesterone has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. Progesterone markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of the limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy.
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ABSTRACT: Background: Although effects of trace elements on secretion of sex steroids and insulin have been studied, the effects of these hormones on serum level of trace elements have been rarely investigated. The aim of the present study was to evaluate the effect of testosterone and finasteride administration and castration on serum levels of testosterone, insulin, zinc and chromium. Methods: Male adult rats (n = 32) were divided into 4 groups (n = 8). Group 1, control; Group 2, castration, castration was done at the first day of the study; Group 3, finasteride (20 mg/kg/day, dissolved in drinking water) and Group 4, testosterone (5 mg/kg/day, i.p.). At the end of the period of the study (35 days), serum testosterone, insulin, zinc and chromium levels were determined in the blood samples collected directly from the right atrium of the heart of the animals. Results: The data indicated that the serum levels of testosterone, insulin and zinc were significantly increased (P<0.01) in testosterone-administrated and finasteride groups, but the level of chromium was decreased in both groups (P<0.01). Castrated group had the lowest serum levels of testosterone, insulin and zinc (P<0.05). Also, the levels of serum chromium in this group were increased. Conclusion: The study demonstrates that testosterone and finasteride increases insulin and zinc levels and decreases chromium levels in the serum of male adult rats. According to these data, it seems that testosterone may affect glucose cycle through effect on serum insulin levels and trace elements such as zinc and chromium.Iranian biomedical journal 01/2013; 17(1):49-53.