Functional characterization of estrogen receptor subtypes, ER{alpha} and ER{beta}, mediating vitellogenin production in the liver of rainbow trout

Journal Article · Mon Oct 15 04:00:00 EDT 2007 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2007.06.017· OSTI ID:21077819

Leanos-Castaneda, Olga ^[1]; Kraak, Glen van der ^[1]

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1. Department of Integrative Biology, University of Guelph, Ontario, N1G 2W1 (Canada)

The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ER{alpha} and ER{beta}, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ER{alpha} selective agonist, methyl-piperidino-pyrazole (MPP) an ER{alpha} selective antagonist, and diarylpropionitrile (DPN) an ER{beta} selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbow trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [{sup 3}H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ER{alpha} could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ER{beta}. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ER{alpha}. On the other hand, once blocked ER{alpha} with MPP, the only manifestation of agonist activity of estradiol would be achieved via ER{beta}. In conclusion, the present results indicate that vitellogenin production is mainly mediated through ER{beta}, implying, furthermore that compounds which only exhibit ER{alpha} selectivity are not detected by vitellogenin bioassay.

• OSTI ID: 21077819
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 224; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOASSAY
BIOLOGICAL INDICATORS
DOSES
ESTRADIOL
LIGANDS
LIVER
LIVER CELLS
PYRAZOLES
RECEPTORS
TAMOXIFEN
TRITIUM
TROUT