Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes

Heather A. Molenda-Figueira, Suzanne D. Murphy, Katherine L. Shea, Nora K. Siegal, Yingxin Zhao, Joseph G. Chadwick, Larry Denner, Marc J. Tetel

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In vitro studies reveal that nuclear receptor coactivators enhance the transcriptional activity of steroid receptors, including estrogen (ER) and progestin receptors (PR), through ligand-dependent interactions. Whereas work from our laboratory and others shows that steroid receptor coactivator-1 (SRC-1) is essential for efficient ER and PR action in brain, very little is known about receptor-coactivator interactions in brain. In the present studies, pull-down assays were used to test the hypotheses that SRC-1 from hypothalamic and hippocampal tissue physically associate with recombinant PR or ER in a ligand-dependent manner. SRC-1, from hypothalamus or hippocampus, interacted with PR-A and PR-B in the presence of an agonist, but not in the absence of ligand or in the presence of a selective PR modulator, RU486. Interestingly, SRC-1 from brain associated more with PR-B, the stronger transcriptional activator, than with PR-A. In addition, SRC-1 from brain, which was confirmed by mass spectrometry, interacted with ERα and ERβ in the presence of agonist but not when unliganded or in the presence of the selective ER modulator, tamoxifen. Furthermore, SRC-1 from hypothalamus, but not hippocampus, interacted more with ERα than ERβ, suggesting distinct expression patterns of other cofactors in these brain regions. These findings suggest that interactions of SRC-1 from brain with PR and ER are dependent on ligand, receptor subtype, and brain region to manifest the pleiotropic functional consequences that underlie steroid-regulated behaviors. The present findings reveal distinct contrasts with previous cell culture studies and emphasize the importance of studying receptor-coactivator interactions using biologically relevant tissue.

Original languageEnglish (US)
Pages (from-to)5272-5279
Number of pages8
JournalEndocrinology
Volume149
Issue number10
DOIs
StatePublished - Oct 2008

Fingerprint

Nuclear Receptor Coactivator 1
Steroid Receptors
Progesterone Receptors
Estrogens
Brain
Ligands
Estrogen Receptors
Hypothalamus
Hippocampus
Nuclear Receptor Coactivators
Tamoxifen
Mass Spectrometry
Cell Culture Techniques
Steroids

ASJC Scopus subject areas

  • Endocrinology

Cite this

Molenda-Figueira, H. A., Murphy, S. D., Shea, K. L., Siegal, N. K., Zhao, Y., Chadwick, J. G., ... Tetel, M. J. (2008). Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes. Endocrinology, 149(10), 5272-5279. https://doi.org/10.1210/en.2008-0048

Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes. / Molenda-Figueira, Heather A.; Murphy, Suzanne D.; Shea, Katherine L.; Siegal, Nora K.; Zhao, Yingxin; Chadwick, Joseph G.; Denner, Larry; Tetel, Marc J.

In: Endocrinology, Vol. 149, No. 10, 10.2008, p. 5272-5279.

Research output: Contribution to journalArticle

Molenda-Figueira, HA, Murphy, SD, Shea, KL, Siegal, NK, Zhao, Y, Chadwick, JG, Denner, L & Tetel, MJ 2008, 'Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes', Endocrinology, vol. 149, no. 10, pp. 5272-5279. https://doi.org/10.1210/en.2008-0048
Molenda-Figueira, Heather A. ; Murphy, Suzanne D. ; Shea, Katherine L. ; Siegal, Nora K. ; Zhao, Yingxin ; Chadwick, Joseph G. ; Denner, Larry ; Tetel, Marc J. / Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes. In: Endocrinology. 2008 ; Vol. 149, No. 10. pp. 5272-5279.
@article{f07e7fed5ba34fd29654303a7f701325,
title = "Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes",
abstract = "In vitro studies reveal that nuclear receptor coactivators enhance the transcriptional activity of steroid receptors, including estrogen (ER) and progestin receptors (PR), through ligand-dependent interactions. Whereas work from our laboratory and others shows that steroid receptor coactivator-1 (SRC-1) is essential for efficient ER and PR action in brain, very little is known about receptor-coactivator interactions in brain. In the present studies, pull-down assays were used to test the hypotheses that SRC-1 from hypothalamic and hippocampal tissue physically associate with recombinant PR or ER in a ligand-dependent manner. SRC-1, from hypothalamus or hippocampus, interacted with PR-A and PR-B in the presence of an agonist, but not in the absence of ligand or in the presence of a selective PR modulator, RU486. Interestingly, SRC-1 from brain associated more with PR-B, the stronger transcriptional activator, than with PR-A. In addition, SRC-1 from brain, which was confirmed by mass spectrometry, interacted with ERα and ERβ in the presence of agonist but not when unliganded or in the presence of the selective ER modulator, tamoxifen. Furthermore, SRC-1 from hypothalamus, but not hippocampus, interacted more with ERα than ERβ, suggesting distinct expression patterns of other cofactors in these brain regions. These findings suggest that interactions of SRC-1 from brain with PR and ER are dependent on ligand, receptor subtype, and brain region to manifest the pleiotropic functional consequences that underlie steroid-regulated behaviors. The present findings reveal distinct contrasts with previous cell culture studies and emphasize the importance of studying receptor-coactivator interactions using biologically relevant tissue.",
author = "Molenda-Figueira, {Heather A.} and Murphy, {Suzanne D.} and Shea, {Katherine L.} and Siegal, {Nora K.} and Yingxin Zhao and Chadwick, {Joseph G.} and Larry Denner and Tetel, {Marc J.}",
year = "2008",
month = "10",
doi = "10.1210/en.2008-0048",
language = "English (US)",
volume = "149",
pages = "5272--5279",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "10",

}

TY - JOUR

T1 - Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes

AU - Molenda-Figueira, Heather A.

AU - Murphy, Suzanne D.

AU - Shea, Katherine L.

AU - Siegal, Nora K.

AU - Zhao, Yingxin

AU - Chadwick, Joseph G.

AU - Denner, Larry

AU - Tetel, Marc J.

PY - 2008/10

Y1 - 2008/10

N2 - In vitro studies reveal that nuclear receptor coactivators enhance the transcriptional activity of steroid receptors, including estrogen (ER) and progestin receptors (PR), through ligand-dependent interactions. Whereas work from our laboratory and others shows that steroid receptor coactivator-1 (SRC-1) is essential for efficient ER and PR action in brain, very little is known about receptor-coactivator interactions in brain. In the present studies, pull-down assays were used to test the hypotheses that SRC-1 from hypothalamic and hippocampal tissue physically associate with recombinant PR or ER in a ligand-dependent manner. SRC-1, from hypothalamus or hippocampus, interacted with PR-A and PR-B in the presence of an agonist, but not in the absence of ligand or in the presence of a selective PR modulator, RU486. Interestingly, SRC-1 from brain associated more with PR-B, the stronger transcriptional activator, than with PR-A. In addition, SRC-1 from brain, which was confirmed by mass spectrometry, interacted with ERα and ERβ in the presence of agonist but not when unliganded or in the presence of the selective ER modulator, tamoxifen. Furthermore, SRC-1 from hypothalamus, but not hippocampus, interacted more with ERα than ERβ, suggesting distinct expression patterns of other cofactors in these brain regions. These findings suggest that interactions of SRC-1 from brain with PR and ER are dependent on ligand, receptor subtype, and brain region to manifest the pleiotropic functional consequences that underlie steroid-regulated behaviors. The present findings reveal distinct contrasts with previous cell culture studies and emphasize the importance of studying receptor-coactivator interactions using biologically relevant tissue.

AB - In vitro studies reveal that nuclear receptor coactivators enhance the transcriptional activity of steroid receptors, including estrogen (ER) and progestin receptors (PR), through ligand-dependent interactions. Whereas work from our laboratory and others shows that steroid receptor coactivator-1 (SRC-1) is essential for efficient ER and PR action in brain, very little is known about receptor-coactivator interactions in brain. In the present studies, pull-down assays were used to test the hypotheses that SRC-1 from hypothalamic and hippocampal tissue physically associate with recombinant PR or ER in a ligand-dependent manner. SRC-1, from hypothalamus or hippocampus, interacted with PR-A and PR-B in the presence of an agonist, but not in the absence of ligand or in the presence of a selective PR modulator, RU486. Interestingly, SRC-1 from brain associated more with PR-B, the stronger transcriptional activator, than with PR-A. In addition, SRC-1 from brain, which was confirmed by mass spectrometry, interacted with ERα and ERβ in the presence of agonist but not when unliganded or in the presence of the selective ER modulator, tamoxifen. Furthermore, SRC-1 from hypothalamus, but not hippocampus, interacted more with ERα than ERβ, suggesting distinct expression patterns of other cofactors in these brain regions. These findings suggest that interactions of SRC-1 from brain with PR and ER are dependent on ligand, receptor subtype, and brain region to manifest the pleiotropic functional consequences that underlie steroid-regulated behaviors. The present findings reveal distinct contrasts with previous cell culture studies and emphasize the importance of studying receptor-coactivator interactions using biologically relevant tissue.

UR - http://www.scopus.com/inward/record.url?scp=53249113569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53249113569&partnerID=8YFLogxK

U2 - 10.1210/en.2008-0048

DO - 10.1210/en.2008-0048

M3 - Article

C2 - 18566116

AN - SCOPUS:53249113569

VL - 149

SP - 5272

EP - 5279

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 10

ER -