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Estrogenic activity of estradiol and its metabolites in the ER‐CALUX assay with human T47D breast cells Note
Author(s) -
HOOGENBOOM L. A. P.,
HAAN L.,
HOOIJERINK D.,
BOR G.,
MURK A. J.,
BROUWER A.
Publication year - 2001
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1034/j.1600-0463.2001.d01-110.x
Subject(s) - estrone , potency , chemistry , estradiol benzoate , bioassay , estrogen , medicine , endocrinology , in vitro , incubation , biological activity , metabolite , stereochemistry , biochemistry , biology , hormone , ovariectomized rat , genetics
A number of metabolites of 17β‐estradiol were tested for their estrogenic activity using the ER‐CALUX assay based on the increased expression of luciferase in exposed T47D breast cancer cells. E 2 β and estrone showed similar potencies in the test, whereas E 2 α was 100 times less active. Incubation of cells with estrone (0.35 μM) resulted in the formation of E 2 β, whereas the reverse reaction was observed for E 2 β. The resulting equilibrium may explain the similar estrogenic potency of estrone in the test. The synthetic 17‐hydroxy benzoate ester of E 2 β was 3 times less active than the parent compound. The 17‐hydroxy palmitate and oleate esters of E 2 β, were respectively 25 and 200 times less active than the parent compound. The 2‐hydroxy metabolites of E 2 β and estrone showed a 5,000 to 10,000 fold lower activity. The 4‐hydroxy metabolites were more potent than the 2‐hydroxy metabolites, showing only a 20–200 times lower activity. The 2‐ and 4‐methoxyesters of estrone were 700 times less active. It is concluded that the estrogenic potency of metabolites formed in cattle after treatment with E 2 β, like estrone, E 2 α and especially the esters of E 2 β, may be significant with respect to the potential risk of the use of estradiol for growth promotion in domestic animals in certain countries.