Abstract
Brain neurosteroids modulate gamma-aminobutyric acid type A (GABA A) receptor activity, thereby playing a role in mood disorders. Alterations in 17β-estradiol (E2) 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 E2 in vitro (C6 glioma cells) and in vivo (mouse brain). The results showed that supraphysiological levels of E2 induced a decrease in the accumulation of both neurosteroids, probably by decreasing the activity of 5αR. We hypothesize that the high levels of E2 in pregnancy attenuate the increase in the conversion of P to THP in the brain and that the ratio of E2/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".
Original language | English |
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Pages (from-to) | 167-172 |
Number of pages | 6 |
Journal | Brain Research |
Volume | 1020 |
Issue number | 1-2 |
DOIs | |
State | Published - 10 Sep 2004 |
Externally published | Yes |
Keywords
- 5α-Reductase
- Allopregnanolone
- Endocrine and autonomic regulation
- Estradiol
- GABA receptor
- Neuroendocrine regulation: other
- Neurosteroids
- Progesterone