Estriol 3-β-D-glucuronide is a metabolite of estriol . It is formed from estriol by the UDP-glucuronosyltransferase (UGT) isoform UGT1A10. Estriol 3-β-D-glucuronide binds to basolateral and canalicular liver plasma membranes with Kd values of 85 and 164 μM, respectively. It competitively inhibits the hydrolysis of 4-methylumbelliferyl-β-D-glucuronide and is a substrate for hydrolysis by Klotho-human IgG1 Fc protein (KLFc).
17-Epiestriol is a metabolite of estrone .1It is formed from estroneviaa 16α-hydroxy estrone intermediate by reduction of the C-17 ketone. 17-Epiestriol binds to estrogen receptor α (ERα) and ERβ with relative binding affinities of 29 and 80 compared with 17β-estradiol .2 1.Brinton, L.A., Trabert, B., Anderson, G.L., et al.Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal womenCancer Epidemiol. Biomarkers Prev.25(7)1081-1089(2016) 2.Kuiper, G.G.J.M., Lemmen, J.G., Carlsson, B., et al.Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor βEndocrinology139(10)4252-4263(1998)
The naturally-occurring estrogens are estrone , estradiol , and estriol . 16α-hydroxy Estrone (16α-OHE1) is a hydroxylated metabolite of E1 as well as an interconversion product with E2. E1 is 16α-hydroxylated by cytochrome P450 (CYP) isoforms, including CYP1A1, CYP3A5, CYP3A4, and CYP3A7, with CYP3A5 being breast-specific. 16α-OHE1 is sulphatized or glucuronidated before excretion. It is increased in rheumatoid arthritis and decreased by physical activity. Unlike the parent estrogens and other hydroxylated metabolites of E1, 16α-OHE1 binds covalently and persistently activates estrogen receptors. In addition, this metabolite increases cell proliferation and does not suppress TNF-α secretion, whereas other estrogen metabolites are not pro-proliferative and have marked effects on TNF-α secretion. The levels of 16α-OHE1 are increased in some forms of hormone therapy. Because hormone therapy increases breast cancer risk, 16α-OHE1 has been implicated as a risk factor for breast cancer, although supportive data remains elusive.