Estrogen receptor specifically decreases dioxin-induced cypia1 in cultured human endometrial cells

M. S. Ricci, W. A. Toscano

Research output: Contribution to journalArticlepeer-review

Abstract

\Vo oxamined whether [igand-bound estrogen receptor exerted regulalory contro] over dioxin-nmdiated cytochrome P450 1AI (CYP1A1) trans(:ription in cultured human endometrial epithelial (:ells (ECC 1). 2,3,7,8-F,t ra(hlorodibenzo-p-dioxin (TCDD) induced CYP 1A 1 monooxygenase activity in a concentration- and time-dependent manner. The half-maximal effeciw, concentration (ECs0) for TCDI) was 1.5 nM. Another Ah receptor agonist, '2 3 7 hq.iachlorodibenzofuran, induced CYP 1A1 activity in a concentrationd(,pcmdent manner, whereas the inactive congener, 2,7 dichlorodibenzo-pdioxin, did not, even at concentrations 1000 times greater than TCDD. Im[ntlll()[)lot analysis confirmed the presence of Ah receptor in ECC-1 cell extract s. These results demonstrated that. human endornetria] cells contain functional Ah receptors. Exposing cultures to saturating concentralions of TCDI) (10 nM) and l?.3-estradiol (l0 nM) simultaneously resulted in a 75 decrease in T(il)l)-induced CYP1AI activity. 17fl-estradiol mediated a decrease of ['(:l)l)-induced CYPIAI mRNA which correlated with loss of enzymatic activity. Addition of estrogen receptor antagonists, 4-hydroxytamoxifen or ICI lg2.?g0, reversed 17/%estradiol action by restoring TCDD-induced CYP1A1 mRNA and activity. Agonists for the progesterone, glhco(orticoid and androgen r-ceptors did not significantly decrease CYP 1AI activity. These data suggest aclivated estrogen receptor specifically modulates Ah receptor-mediated induction of ('YP1A1 and may have important implications for endometrial (ell re$nlal ion.

Original languageEnglish (US)
Pages (from-to)A1328
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

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