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

Rachel Maayan*, Benjamin Fisch, Moran Galdor, Boris Kaplan, Nili Shinnar, Noa Kinor, Ella Zeldich, Avi Valevski, Abraham Weizman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)167-172
Number of pages6
JournalBrain Research
Volume1020
Issue number1-2
DOIs
StatePublished - 10 Sep 2004
Externally publishedYes

Funding

FundersFunder number
Israeli National Institute of Psychobiology
Tel Aviv University

    Keywords

    • 5α-Reductase
    • Allopregnanolone
    • Endocrine and autonomic regulation
    • Estradiol
    • GABA receptor
    • Neuroendocrine regulation: other
    • Neurosteroids
    • Progesterone

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