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

doi:10.1016/j.brainres.2004.06.025

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

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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
Pages (from-to)	167-172
Number of pages	6
Journal	Brain Research
Volume	1020
Issue number	1-2
DOIs	https://doi.org/10.1016/j.brainres.2004.06.025
State	Published - 10 Sep 2004

Bibliographical note

Funding Information:
This study was supported by grant No. 18-99 of the Israeli National Institute of Psychobiology, Jerusalem, Israel, and a grant from Adams Super Center for Brain Research, Tel Aviv University, Israel (2001–2002).

Funding

This study was supported by grant No. 18-99 of the Israeli National Institute of Psychobiology, Jerusalem, Israel, and a grant from Adams Super Center for Brain Research, Tel Aviv University, Israel (2001–2002).

Funders	Funder 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

Access to Document

10.1016/j.brainres.2004.06.025

Cite this

Maayan, R., Fisch, B., Galdor, M., Kaplan, B., Shinnar, N., Kinor, N., Zeldich, E., Valevski, A., & Weizman, A. (2004). 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. Brain Research, 1020(1-2), 167-172. https://doi.org/10.1016/j.brainres.2004.06.025

@article{d5e51f91036343dd943b43d2d1dc6138,

title = "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 (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{"}.",

keywords = "5α-Reductase, Allopregnanolone, Endocrine and autonomic regulation, Estradiol, GABA receptor, Neuroendocrine regulation: other, Neurosteroids, Progesterone",

author = "Rachel Maayan and Benjamin Fisch and Moran Galdor and Boris Kaplan and Nili Shinnar and Noa Kinor and Ella Zeldich and Avi Valevski and Abraham Weizman",

note = "Funding Information: This study was supported by grant No. 18-99 of the Israeli National Institute of Psychobiology, Jerusalem, Israel, and a grant from Adams Super Center for Brain Research, Tel Aviv University, Israel (2001–2002). ",

year = "2004",

month = sep,

day = "10",

doi = "10.1016/j.brainres.2004.06.025",

language = "אנגלית",

volume = "1020",

pages = "167--172",

journal = "Brain Research",

issn = "0006-8993",

publisher = "Elsevier",

number = "1-2",

}

Maayan, R, Fisch, B, Galdor, M, Kaplan, B, Shinnar, N, Kinor, N, Zeldich, E, Valevski, A & Weizman, A 2004, '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', Brain Research, vol. 1020, no. 1-2, pp. 167-172. https://doi.org/10.1016/j.brainres.2004.06.025

TY - JOUR

T1 - Influence of 17β-estradiol on the synthesis of reduced neurosteroids in the brain (in vivo) and in glioma cells (in vitro)

T2 - Possible relevance to mental disorders in women

AU - Maayan, Rachel

AU - Fisch, Benjamin

AU - Galdor, Moran

AU - Kaplan, Boris

AU - Shinnar, Nili

AU - Kinor, Noa

AU - Zeldich, Ella

AU - Valevski, Avi

AU - Weizman, Abraham

N1 - Funding Information: This study was supported by grant No. 18-99 of the Israeli National Institute of Psychobiology, Jerusalem, Israel, and a grant from Adams Super Center for Brain Research, Tel Aviv University, Israel (2001–2002).

PY - 2004/9/10

Y1 - 2004/9/10

N2 - 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".

AB - 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".

KW - 5α-Reductase

KW - Allopregnanolone

KW - Endocrine and autonomic regulation

KW - Estradiol

KW - GABA receptor

KW - Neuroendocrine regulation: other

KW - Neurosteroids

KW - Progesterone

UR - http://www.scopus.com/inward/record.url?scp=4143121067&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2004.06.025

DO - 10.1016/j.brainres.2004.06.025

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 15312799

AN - SCOPUS:4143121067

SN - 0006-8993

VL - 1020

SP - 167

EP - 172

JO - Brain Research

JF - Brain Research

IS - 1-2

ER -

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

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this