Estriol is a Stronger Transcriptional Activator than is either 17β-Estradiol or Estrone of Human and Elephant Shark Estrogen Receptor-alpha and Estrogen Receptor-beta transfected into COS-7 Cells.

Humans and other vertebrates contain two estrogen receptors (ERs), ERα and ERβ, 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 ERα and ERβ, E1 is next most active, followed by E3. We studied transcriptional activation of human ERα and ERβ 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 embryonic kidney (HEK-293) cells. To our surprise, in COS-7 cells, E3 had the lowest half-maximal response (EC50) for human ERα and ERβ than either E2, which was second most active estrogen, or E1. In contrast, for human ERα and ERβ 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 ERα and ERβ. 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.