[Competitive binding of some alkyl p-hydroxybenzoates to human estrogen receptor alpha and beta].
Alkyl p-hydroxybenzoates such as isobutyl p-hydroxybenzoate (PHBA-iBu), butyl p-hydroxybenzoate (PHBA-nBu), isopropyl p-hydroxybenzoate (PHBA-iPr), propyl p-hydroxybenzoate (PHBA-nPr), ethyl p-hydroxybenzoate (PHBA-Et), and methyl p-hydroxybenzoate (PHBA-Me) are widely used as preservatives, stabilizers and antiseptics for medical supplies, cosmetics, foodstuffs etc. We determined the binding affinity of alkyl p-hydroxybenzoates to human estrogen receptor alpha (ER alpha) and beta (ER beta) by non-RI receptor binding assays. PHBA-iBu had a high binding affinity for ER alpha (IC50: 6.0 x 10(-6) M, the relative binding affinity (RBA): 0.267) and ER beta (IC50: 5.0 x 10(-6) M, RBA: 0.340). These IC50 values and RBA were almost the same as those of bisphenol A. The ranking of the estrogenic potency of alkyl p-hydroxybenzoates for both ERs is different; that is, PHBA-iBu > PHBA-nBu[symbol: see text]PHBA-iPr[symbol: see text]PHBA-nPr > PHBA-Et >> PHBA-Me. Alkyl p-hydroxybenzoates bound with equal relative affinity to both ER alpha and beta proteins. Alkyl p-hydroxybenzoate having a long alkyl side-chain showed a high affinity for ER alpha and beta. These findings suggest that p-hydroxybenzoates may be endocrine disruptors.
Satoh
K
K
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Nagai
F
F
Aoki
N
N
Nishijima
M
M
D001667:Binding, Competitive; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006801:Humans; D010226:Parabens / Q000737:chemistry / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010226:Parabens; D011960:Receptors, Estrogen; C038193:4-hydroxybenzoic acid