Influence of 17β-estradiol on the synthesis of reduced neurosteroids in the brain (in vivo) and in glioma cells (in vitro): possible relevance to mental disorders in women

Abstract

Brain neurosteroids modulate gamma-aminobutyric acid type A (GABA A) receptor activity, thereby playing a role in mood disorders. Alterations in 17β-estradiol (E 2) and progesterone (P) are also known to play a significant role in psychopathology in women. The aim of the present study was to evaluate the synthesis of dihydroprogesterone (DHP), tetrahydroprogesterone (THP), and the activity of 5α-reductase (5αR) which regulates the reduction of P to DHP on exposure to supraphysiological levels of E 2 in vitro (C6 glioma cells) and in vivo (mouse brain). The results showed that supraphysiological levels of E 2 induced a decrease in the accumulation of both neurosteroids, probably by decreasing the activity of 5αR. We hypothesize that the high levels of E 2 in pregnancy attenuate the increase in the conversion of P to THP in the brain and that the ratio of E 2/P modulates the sedative effect of THP. This process may be relevant to psychopathological disorders that are ascribed to drastic alterations in estrogen levels, such as premenstrual syndrome, pregnancy-related mental disorders, and postpartum “blues”.