Abstract
Steroid hormones are a key regulator of reproductive biology in vertebrates, and are largely regulated via nuclear receptor families. Estrogen signaling is regulated by two estrogen receptor (ER) subtypes alpha and beta in the nucleus. In order to understand the role of estrogen in vertebrates, these ER from various species have been isolated and were functionally analyzed using luciferase reporter gene assays. Interestingly, species difference in estrogen sensitivity has been noted in the past, and it was reported that snake ER displayed highest estrogen sensitivity. Here, we isolated additional ER from three lizards: chameleon (Bradypodion pumilum), skink (Plestiodon finitimus), and gecko (Gekko japonicus). We have performed functional characterization of these ERs using reporter gene assay system, and found high estrogen sensitivity in all three species. Furthermore, comparison with results from other tetrapod ER revealed a seemingly uniform gradual pattern of ligand sensitivity evolution. In silico 3D homology modeling of the ligand-binding domain revealed structural variation at three sites, helix 2, and juncture between helices 8 and 9, and caudal region of helix 10/11. Docking simulations indicated that predicted ligand-receptor interaction also correlated with the reporter assay results, and overall squamates displayed highest stabilized interactions. The assay system and homology modeling system provides tool for in-depth comparative analysis of estrogen function, and provides insight toward the evolution of ER among vertebrates.
| Original language | English |
|---|---|
| Pages (from-to) | 88-95 |
| Number of pages | 8 |
| Journal | General and Comparative Endocrinology |
| Volume | 238 |
| DOIs | |
| Publication status | Published - Nov 1 2016 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Animal Science and Zoology
- Endocrinology
Cite this
Characterization of evolutionary trend in squamate estrogen receptor sensitivity. / Yatsu, Ryohei; Katsu, Yoshinao; Kohno, Satomi; Mizutani, Takeshi; Ogino, Yukiko; Ohta, Yasuhiko; Myburgh, Jan; van Wyk, Johannes H.; Guillette, Louis J.; Miyagawa, Shinichi; Iguchi, Taisen.
In: General and Comparative Endocrinology, Vol. 238, 01.11.2016, p. 88-95.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of evolutionary trend in squamate estrogen receptor sensitivity
AU - Yatsu, Ryohei
AU - Katsu, Yoshinao
AU - Kohno, Satomi
AU - Mizutani, Takeshi
AU - Ogino, Yukiko
AU - Ohta, Yasuhiko
AU - Myburgh, Jan
AU - van Wyk, Johannes H.
AU - Guillette, Louis J.
AU - Miyagawa, Shinichi
AU - Iguchi, Taisen
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Steroid hormones are a key regulator of reproductive biology in vertebrates, and are largely regulated via nuclear receptor families. Estrogen signaling is regulated by two estrogen receptor (ER) subtypes alpha and beta in the nucleus. In order to understand the role of estrogen in vertebrates, these ER from various species have been isolated and were functionally analyzed using luciferase reporter gene assays. Interestingly, species difference in estrogen sensitivity has been noted in the past, and it was reported that snake ER displayed highest estrogen sensitivity. Here, we isolated additional ER from three lizards: chameleon (Bradypodion pumilum), skink (Plestiodon finitimus), and gecko (Gekko japonicus). We have performed functional characterization of these ERs using reporter gene assay system, and found high estrogen sensitivity in all three species. Furthermore, comparison with results from other tetrapod ER revealed a seemingly uniform gradual pattern of ligand sensitivity evolution. In silico 3D homology modeling of the ligand-binding domain revealed structural variation at three sites, helix 2, and juncture between helices 8 and 9, and caudal region of helix 10/11. Docking simulations indicated that predicted ligand-receptor interaction also correlated with the reporter assay results, and overall squamates displayed highest stabilized interactions. The assay system and homology modeling system provides tool for in-depth comparative analysis of estrogen function, and provides insight toward the evolution of ER among vertebrates.
AB - Steroid hormones are a key regulator of reproductive biology in vertebrates, and are largely regulated via nuclear receptor families. Estrogen signaling is regulated by two estrogen receptor (ER) subtypes alpha and beta in the nucleus. In order to understand the role of estrogen in vertebrates, these ER from various species have been isolated and were functionally analyzed using luciferase reporter gene assays. Interestingly, species difference in estrogen sensitivity has been noted in the past, and it was reported that snake ER displayed highest estrogen sensitivity. Here, we isolated additional ER from three lizards: chameleon (Bradypodion pumilum), skink (Plestiodon finitimus), and gecko (Gekko japonicus). We have performed functional characterization of these ERs using reporter gene assay system, and found high estrogen sensitivity in all three species. Furthermore, comparison with results from other tetrapod ER revealed a seemingly uniform gradual pattern of ligand sensitivity evolution. In silico 3D homology modeling of the ligand-binding domain revealed structural variation at three sites, helix 2, and juncture between helices 8 and 9, and caudal region of helix 10/11. Docking simulations indicated that predicted ligand-receptor interaction also correlated with the reporter assay results, and overall squamates displayed highest stabilized interactions. The assay system and homology modeling system provides tool for in-depth comparative analysis of estrogen function, and provides insight toward the evolution of ER among vertebrates.
UR - http://www.scopus.com/inward/record.url?scp=84992188050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992188050&partnerID=8YFLogxK
U2 - 10.1016/j.ygcen.2016.04.005
DO - 10.1016/j.ygcen.2016.04.005
M3 - Article
C2 - 27072832
AN - SCOPUS:84992188050
VL - 238
SP - 88
EP - 95
JO - General and Comparative Endocrinology
JF - General and Comparative Endocrinology
SN - 0016-6480
ER -