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bioRxiv · 10.64898/2026.07.03.736429

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

Ao, Y.·Cabizares, R. M. d. R.·Baker, M. E.·Katsu, Y.
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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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Ao, Y., Cabizares, R. M. d. R., Baker, M. E., Katsu, Y.. 2026-07-09. 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. https://doi.org/10.64898/2026.07.03.736429

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