THE RODENT UTEROTROPHIC ASSAY : CRITICAL PROTOCOL FEATURES, STUDIES WITH NONYLPHENOLS, COMPARISON WITH A YEAST ESTROGENICITY ASSAY by
نویسندگان
چکیده
2 SUMMARY The major protocol features of the immature rat uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used and the specificity of the assay for estrogens. It is concluded that three daily oral DGPLQLVWUDWLRQVRIWHVWFKHPLFDOVWRG old rats, followed by determination of absolute uterus weights on the fourth day, provides a sensitive and toxicologically relevant in vivo estrogenicity assay. Rats are favoured over mice for reasons of toxicological practice, but the choice of test species is probably not a critical protocol variable, as evidenced by the similar sensitivity of rats and mice to the uterotrophic activity of methoxychlor. Vaginal opening is VKRZQWREHDXVHIXOEXWQRQGHILQLWLYHDG chemicals to reduce or abolish the uterotrophic response of estradiol is suggested to provide a useful extension of the uterotrophic assay foUWKHSXUSRVHRIGHWHFWLQJ The results of a series of studies on the environmental estrogen nonylphenol (NP), and its OLQHDU LVRPHU QQRQ\OSKHQRO FRQILUP WKDW EU ng of the aliphatic sidechain is important for activity. 17 'HVR[\HVWUDGLRO LV VKRZQ WR EH RI similar activity to estradiol in the uterotrophic assay, and is suggested to represent the 'parent' estrogen of NP. Benzoylation of 13 DQG GHVR[\HVWUDGLRO GLG QRW DIIHFW W r uterotrophic activity, in contrast to the enhancing effect of benzoylation on estradiol. Selected chemicals shown to be active in the immature rat uterotrophic assay were also evaluated in an in vitro yeast human estrogen receptor transactivation assay. Most of the chemicals gave similar qualitative responses to those seen in the uterotrophic assay, and the detection of the estrogen methoxychlor by the yeast assay evidenced a degree of intrinsic metabolic competence. However, the assay had a reduced ability (compared to rodents) to hydrolyse the benzoate ester of estradiol, and the estrogenic benzoate derivative of NP was not active in the yeast assay. These last results indicate that current metabolic deficiencies of in vitro estrogenicity assays will limit the value of negative data for the immediate future. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and confirm the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.
منابع مشابه
Increasing the sensitivity of the rodent uterotrophic assay to estrogens, with particular reference to bisphenol A.
The gravimetric uterotrophic assay is currently the most well-established, short-term rodent estrogenicity assay. Increasing attention is being paid to the extent to which use of morphometric or molecular changes in the uterus could act as surrogates for the gravimetric end point of the assay, thereby perhaps increasing the sensitivity of the assay. In this paper I discuss the available data, p...
متن کاملExtending an in vitro panel for estrogenicity testing: the added value of bioassays for measuring antiandrogenic activities and effects on steroidogenesis.
In the present study, a previously established integrated testing strategy (ITS) for in vitro estrogenicity testing was extended with additional in vitro assays in order to broaden its sensitivity to different modes of action resulting in apparent estrogenicity, i.e., other than estrogen receptor (ER) binding. To this end, an extra set of 10 estrogenic compounds with modes of action in part dif...
متن کاملThe intact immature rodent uterotrophic bioassay: possible effects on assay sensitivity of vomeronasal signals from male rodents and strain differences.
The vomeronasal organ in rodents is an important social and sexual signaling pathway. We have investigated whether the housing of intact immature females in close proximity to mature males would interfere with the sensitivity of the immature rodent uterotrophic bioassay as the result of vomeronasal signals transmitted by male urinary proteins. The hypothesis was that the proximity of males migh...
متن کاملThe mouse uterotrophic assay: a reevaluation of its validity in assessing the estrogenicity of bisphenol A.
The prevalence of synthetic chemicals in our environment that are capable of mimicking the female hormone estrogen is a growing concern. One such chemical, bisphenol A (BPA), has been shown to leach from a variety of resin-based and plastic products, including dental sealants and food and beverage containers, in concentrations that are sufficient to induce cell proliferation in vitro. The respo...
متن کاملA 155-plex high-throughput in vitro coregulator binding assay for (anti-)estrogenicity testing evaluated with 23 reference compounds.
To further develop an integrated in vitro testing strategy for replacement of in vivo tests for (anti-)estrogenicity testing, the ligand-modulated interaction of coregulators with estrogen receptor α was assessed using a PamChip® plate. The relative estrogenic potencies determined, based on ERα binding to coregulator peptides in the presence of ligands on the PamChip® plate, were compared to th...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2006