Estriol is a Stronger Transcriptional Activator than is either 17beta-Estradiol or Estrone of Hu-man and Elephant Shark Estrogen Receptor-alpha and Estrogen Receptor-beta transfected into COS-7 Cells
- 1Hokkaido University
Abstract
Humans and other vertebrates contain two estrogen receptors (ERs), ER-alpha and ER-beta, which mediate the physiological actions of three estrogens: estrone (E1), estradiol (E2) and estriol (E3). Of these three estrogens, in vivo, E2 is the strongest transcriptional activator of ER-alpha and ER-beta, E1 is next most active, followed by E3. We studied transcriptional activation of human ER-alpha and ER-beta by E2, E1 and E3 in African green monkey kidney (COS-7) cells, which we compared with studies of estrogen stimulation of ER transcription in human em-bryonic kidney (HEK-293) cells. To our surprise, in COS-7 cells, E3 had the lowest half-maximal response (EC50) for human ER-alpha and ER-beta than either E2, which was second most active estrogen, or E1. In contrast, for human ER-alpha and ER-beta transfected into HEK-293 cells, E2 was the most active estrogen, followed by E1 and E3. Similar results were found in COS-7 cells and HEK-293 cells transfected with elephant shark ER-alpha and ER-beta. Thus, under some conditions, E3 is a more active estrogen than either E2 or E1. This suggests that E3 may be a novel physiological ligand for the ER in some mammalian cells, including the placenta, where E3 levels increase substantially during pregnancy.
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BibTeX
@misc{ao2026estriol,
title = {{Estriol is a Stronger Transcriptional Activator than is either 17beta-Estradiol or Estrone of Hu-man and Elephant Shark Estrogen Receptor-alpha and Estrogen Receptor-beta transfected into COS-7 Cells}},
author = {Y. Ao and R. M. d. R. Cabizares and M. E. Baker and Y. Katsu},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.03.736429},
url = {https://www.biorxiv.org/content/10.64898/2026.07.03.736429v2},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Estriol is a Stronger Transcriptional Activator than is either 17beta-Estradiol or Estrone of Hu-man and Elephant Shark Estrogen Receptor-alpha and Estrogen Receptor-beta transfected into COS-7 Cells
AU - Y. Ao
AU - R. M. d. R. Cabizares
AU - M. E. Baker
AU - Y. Katsu
PY - 2026
DA - 2026/07/03
PB - bioRxiv
DO - 10.64898/2026.07.03.736429
UR - https://www.biorxiv.org/content/10.64898/2026.07.03.736429v2
AB - Humans and other vertebrates contain two estrogen receptors (ERs), ER-alpha and ER-beta, which mediate the physiological actions of three estrogens: estrone (E1), estradiol (E2) and estriol (E3). Of these three estrogens, in vivo, E2 is the strongest transcriptional activator of ER-alpha and ER-beta, E1 is next most active, followed by E3. We studied transcriptional activation of human ER-alpha and ER-beta by E2, E1 and E3 in African green monkey kidney (COS-7) cells, which we compared with studies of estrogen stimulation of ER transcription in human em-bryonic kidney (HEK-293) cells. To our surprise, in COS-7 cells, E3 had the lowest half-maximal response (EC50) for human ER-alpha and ER-beta than either E2, which was second most active estrogen, or E1. In contrast, for human ER-alpha and ER-beta transfected into HEK-293 cells, E2 was the most active estrogen, followed by E1 and E3. Similar results were found in COS-7 cells and HEK-293 cells transfected with elephant shark ER-alpha and ER-beta. Thus, under some conditions, E3 is a more active estrogen than either E2 or E1. This suggests that E3 may be a novel physiological ligand for the ER in some mammalian cells, including the placenta, where E3 levels increase substantially during pregnancy.
ER -