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Studies on the physiological effects of estrogen-like compounds in certain forage plants, and of diethylstilbestrol on the laboratory mouse and rat. Ostrovsky, Daniel

Abstract

The physiological effects of partially purified estrogenic extracts from forage plants of widespread economic importance have been studied, using the laboratory mouse and rat as experimental animals. The main purpose of these studies was to compare physiological activities of estrogenic substances from plants with those of a well known synthetic estrogen, diethylstilbestrol (D.E.S.). The latter, like many of the "natural" animal estrogens, is well known to influence the fundamental processes of animal production namely, reproduction, lactation, and growth. The estrogenic treatments were administered orally, either mixed with the diet, or by means of a rubber catheter. Dosage levels were in most cases designed with the grazing animal in mind, so as to allow some opportunity for tentative extrapolations of the results to farm animals which are the chief consumers of estrogen-like substances in forage plants. Red clover estrogenic extracts were used mainly, although some effects of subterranean clover, and birdsfoot trefoil are discussed. Non estrogenic timothy grass extracts were used to help control the experimental conditions. No effect of red clover "estrogens" on Maternal Performance of lactating mice as determined by the total weights of their litters at 12 days was detected. Performances calculated on the basis of 17th day total litter weights appeared to be adversely affected although not to the same extent as a similar level of D.E.S. The high estrogenic content of the diet is believed responsible for this result. Red clover "estrogens" induced increased testes weights, decreased seminal vesicle weights and lowered fertility in intact male mice. Remarkable recovery to normal, of these organs took place within eight days after cessation of estrogenic treatment. Some differences both in genital organ weights, and fertility data between males weaned from normally fed dams and those weaned from dams receiving estrogenic materials throughout the lactation period were observed. Per cent fertility data from females were essentially similar. The effects of red clover "estrogens" on uterine weight and histology, in intact, ovariectomized, hypophysectomized, and hypophysectomized-ovariectomized rats were studied. The absence of the hypophysis, and, or, the ovary does not interfere with the rate or degree of uterine response. The histology of uteri from "estrogen" treated animals is discussed in relation to fertilization, and implantation i.e. fertility. Method of administration of red clover "estrogens" influences the physiological effectiveness of a given dose. When mixed with feed their effect is more marked in terms of uterine response than when the same quantity is administered orally by means of a catheter, in two equal portions, twice daily. Once daily catheterization is even less effective. These results are discussed in relation to quantitative comparisons between injected or implanted doses of "natural" animal estrogens and D.E.S., and the quantities of estrogenic materials likely to be consumed by a grazing animal. Finally, red clover estrogenic extract from 8.4. gm. of dry ground forage increased thyroid uptake of radioactive sodium iodide (I¹³¹ ) in ovariectomized rats with a mean weight of 110 gm. Scintillation count data were confirmed by histological examination of carefully prepared thyroid sections. The likely endocrinological interpretation of this observation is discussed.

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