A Case of a Laboratory Animal Feed with High Estrogenic Activity and Its Impact on in Vivo Responses to Exogenously Administered Estrogens

Abstract

We recently noted that immature rats failed to exhibit a normal uterine response to exogenously administered estradiol as assessed by both biochemical (induction of gene expression) and morphological (altered uterine and vaginal histology, and size) end points. An initial analysis suggested that this was due to a high degree ofestrogenization from a dietary source which was producing a near maximal uterotrophic response prior to hormone treatment. Subsequent chemical analysis indicated that the feed in question contained high amounts of two well-known phytoestrogens, genistein (210 mglkg) and daidzen (14 mg/kg), and the lot of feed in question produced a large uterotrophic ect when fed to immature ovariectomized rats. These findings illustrate that, despite increased awareness of phytoestrogens, some batches of animal feed contain very high amounts of estrogenic components which have marked efects on in vivo end points of hormone action. These observations have important implications for both basic research and screenin methods that utilize in uivo approaches.

Neurobehavioral effects of dietary soy phytoestrogens

“…For example, phytoestrogens mimic estrogen hormone action by decreasing prostate and body weight in males and females while delaying the onset of puberty presumably by blocking estrogen hormone action without impacting cyclicity [72,78]. Our findings are similar to that of a recent study (using a similar concentration of total isoflavones in the diet) that demonstrated high estrogenic activity from dietary phytoestrogens that interfered with a normal uterine response to exogenously administered estradiol [16].…”

“…In this diet, soymeal is the first ingredient listed in the formulation (and the diet does not contain alfalfa). The total isoflavone concentration of the diet we used is similar to that reported in a separate study (approximately 350 mg/g diet of total isoflavones) that was found to have estrogenic activity in rodents [16]. We have compared the influence of this commercial diet to that of a custom diet with very low concentrations of phytoestrogens (Ziegler Brothers, Gardner, PA, USA) [24,105].…”

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

“…This phytoestrogen has 10 2 -fold greater estrogenicity (Bickoff et al, 1962) than soy isoflavones, and major rodent diet manufacturers now offer phytoestrogen-reduced diets that exclude alfalfa as an ingredient. It was pointed out recently that immature rats unwittingly fed a rodent diet formulated with soy-meal and alfalfa had a near maximal uterotrophic stimulation and consequently failed to show the usual biochemical and morphological responses to exogenously administered estradiol (Boettger-Tong et al, 1998). The diet's composition had been reformulated without any notice to researchers using the feed, triggering months of troubleshooting.…”

“…Such effects have tremendous implications for animal experiments, particularly when biochemical or morphological end-points are being measured that may be influenced by the hormonal or nonhormonal properties of isoflavones (Boettger-Tong et al, 1998;Drane et al, 1975). Coumestrol, a component of alfalfa (Knuckles et al, 1976) and still present in some commercial rodent diets, influences uterine growth (Ashby et al, 1999;, accelerates vaginal opening , and causes long-term effects on reproductive cycling and behavior (Whitten et al, 1995).…”

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

“…It was found that soy isoflavones present in feed at high amounts interfere with the value of animal models and with experimental results (10). An example of this was a decreased sensitivity of immature rats (5) and hamsters (20) in the uterotrophic bioassay.…”