The action of dietary phytochemicals quercetin, catechin, resveratrol and naringenin on estrogen-mediated gene expression.
Hepatic expression of apolipoprotein (apo) II is in part modulated by estrogen-mediated stabilization of its mRNA. This stabilization is due to the estrogen-regulated mRNA stabilizing factor (E-RmRNASF) expressed in the liver in response to estrogen (Ratnasabapathy, 1995, Cell. Mol. Biol. Res, 41: 583-594). E-RmRNASF protects the RNA from targeted endonucleolytic degradation. The hepatic expression of E-RmRNASF is modulated by certain estrogenic and antiestrogenic nonsteroidal environmental xenobiotics (Ratnasabapathy et al. 1997, Biochem. Pharmacol., 53: 1425-1434). To determine whether dietary phytochemicals purported to prevent hormone-dependent breast and prostate cancers, and atherosclerosis, acted via the estrogen-cell-signaling pathway, roosters were administered increasing doses up to 1 mmole/kg of resveratrol, quercetin, catechin or naringenin parenterally and tested for hepatic expression of E-RmRNASF. Besides estrogen, the expression of E-RmRNASF in the liver was stimulated by resveratrol and catechin, indicating these agents to be estrogenic. A lack of E-RmRNASF expression was seen with the roosters treated with the vehicle, naringenin or quercetin. To determine whether the agents exerted partial agonistic or antagonistic effects, roosters were administered combinations of estrogen and increasing doses of the above phytochemicals. Resveratrol showed agonistic activity at all concentrations (10-1000 micromol/kg) tested. Catechin showed partial agonistic activity, while quercetin and naringenin appeared to be antagonistic.
Ratna
Warren N
WN
Division of Pharmacology, Toxicology and Medicinal Chemistry, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, NY 11201, USA. WNRatna@aol.com
Simonelli
Joan A
JA
D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis / Q000235:genetics*; D002392:Catechin / Q000494:pharmacology; D002645:Chickens; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000819:agonists / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D028321:Plant Preparations / Q000494:pharmacology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D011794:Quercetin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D001053:Apolipoproteins; D004338:Drug Combinations; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D044950:Flavanones; D005419:Flavonoids; D028321:Plant Preparations; D011498:Protein Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D013267:Stilbenes; C054949:apolipoprotein II; D004958:Estradiol; D002392:Catechin; D011794:Quercetin; C005273:naringenin; D000077185:Resveratrol