Abstract
Phytoestrogens are assumed to affect the endocrine system of animal species similarly to other man-made endocrine disrupters and to exert their effects through estrogen receptors, specifically ERα and ERβ. However, these molecular mechanisms are not fully understood. In this study, 19 phytochemicals were surveyed for agonist and antagonist activities of ERα and ERβ using an ERE-luciferase reporter assay. The results showed that ferutinine is an agonist for ERα and an agonist/antagonist for ERβ, tschimgine is an agonist for both ERα and ERβ, and tschimganidine is an agonist for only ERα. Ferutinine and tschimganidine are sesquiterpenoids, and tschimgine is a monoterpenoid derived from the Umbelliferae family. A competitive binding assay showed that ferutinine has higher binding affinities than tamoxifen for both ERs. Cotransfections of coactivators such as SRC-1, TIF2, AIB1, and TRAP220 in 293T cells and use of the luciferase assay revealed that TRAP220 failed to enhance the transcription mediated by ERβ in the presence of ferutinine. Moreover, a GST pull-down assay showed that TRAP220 marginally bound to ERβ ligand binding domain in the presence of ferutinine. These results suggest that the conformation of ferutinine-liganded ERβ is difficult for TRAP220 to recognize. Taken together, this suggests that some terpenoids can modulate estrogen signaling as ER subtype-selective phytoestrogens similar to SERMs (selective estrogen receptor modulators).
| Original language | English |
|---|---|
| Pages (from-to) | 354-360 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 291 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 1 2002 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Terpenoids found in the Umbelliferae family act as agonists/antagonists for ERα and ERβ : Differential transcription activity between ferutinine-liganded ERα and ERβ. / Ikeda, Kazuhiro; Arao, Yukitomo; Otsuka, Hiroko; Nomoto, Satoshi; Horiguchi, Hyogo; Kayama, Fujio; Ikeda, Kazuhiro; Kato, Shigeaki; Kayama, Fujio; Kato, Shigeaki.
In: Biochemical and Biophysical Research Communications, Vol. 291, No. 2, 01.01.2002, p. 354-360.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Terpenoids found in the Umbelliferae family act as agonists/antagonists for ERα and ERβ
T2 - Differential transcription activity between ferutinine-liganded ERα and ERβ
AU - Ikeda, Kazuhiro
AU - Arao, Yukitomo
AU - Otsuka, Hiroko
AU - Nomoto, Satoshi
AU - Horiguchi, Hyogo
AU - Kayama, Fujio
AU - Ikeda, Kazuhiro
AU - Kato, Shigeaki
AU - Kayama, Fujio
AU - Kato, Shigeaki
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Phytoestrogens are assumed to affect the endocrine system of animal species similarly to other man-made endocrine disrupters and to exert their effects through estrogen receptors, specifically ERα and ERβ. However, these molecular mechanisms are not fully understood. In this study, 19 phytochemicals were surveyed for agonist and antagonist activities of ERα and ERβ using an ERE-luciferase reporter assay. The results showed that ferutinine is an agonist for ERα and an agonist/antagonist for ERβ, tschimgine is an agonist for both ERα and ERβ, and tschimganidine is an agonist for only ERα. Ferutinine and tschimganidine are sesquiterpenoids, and tschimgine is a monoterpenoid derived from the Umbelliferae family. A competitive binding assay showed that ferutinine has higher binding affinities than tamoxifen for both ERs. Cotransfections of coactivators such as SRC-1, TIF2, AIB1, and TRAP220 in 293T cells and use of the luciferase assay revealed that TRAP220 failed to enhance the transcription mediated by ERβ in the presence of ferutinine. Moreover, a GST pull-down assay showed that TRAP220 marginally bound to ERβ ligand binding domain in the presence of ferutinine. These results suggest that the conformation of ferutinine-liganded ERβ is difficult for TRAP220 to recognize. Taken together, this suggests that some terpenoids can modulate estrogen signaling as ER subtype-selective phytoestrogens similar to SERMs (selective estrogen receptor modulators).
AB - Phytoestrogens are assumed to affect the endocrine system of animal species similarly to other man-made endocrine disrupters and to exert their effects through estrogen receptors, specifically ERα and ERβ. However, these molecular mechanisms are not fully understood. In this study, 19 phytochemicals were surveyed for agonist and antagonist activities of ERα and ERβ using an ERE-luciferase reporter assay. The results showed that ferutinine is an agonist for ERα and an agonist/antagonist for ERβ, tschimgine is an agonist for both ERα and ERβ, and tschimganidine is an agonist for only ERα. Ferutinine and tschimganidine are sesquiterpenoids, and tschimgine is a monoterpenoid derived from the Umbelliferae family. A competitive binding assay showed that ferutinine has higher binding affinities than tamoxifen for both ERs. Cotransfections of coactivators such as SRC-1, TIF2, AIB1, and TRAP220 in 293T cells and use of the luciferase assay revealed that TRAP220 failed to enhance the transcription mediated by ERβ in the presence of ferutinine. Moreover, a GST pull-down assay showed that TRAP220 marginally bound to ERβ ligand binding domain in the presence of ferutinine. These results suggest that the conformation of ferutinine-liganded ERβ is difficult for TRAP220 to recognize. Taken together, this suggests that some terpenoids can modulate estrogen signaling as ER subtype-selective phytoestrogens similar to SERMs (selective estrogen receptor modulators).
UR - http://www.scopus.com/inward/record.url?scp=0036295876&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036295876&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2002.6446
DO - 10.1006/bbrc.2002.6446
M3 - Article
C2 - 11846412
AN - SCOPUS:0036295876
VL - 291
SP - 354
EP - 360
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -