Age as a modifying factor of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in the lewis rat.
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9,10-Dimethyl-1,2-benzanthracene↗
Biomedical subjects
S Z Haslam
Publications and source records attributed to S Z Haslam.
Progesterone receptors in normal mammary glands of mice: characterization and relationship to development.
Although progesterone receptors have been characterized in a number of target tissues for progesterone, including some mammary tumors, relatively little is known about these receptors in normal mammary tissues. In the present study using R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), a synthetic progestin, we have identified and characterized the cytoplasmic progesterone receptors in normal mammary glands of mice. The receptor had a high binding affinity (Kd = 2.8 X 10(-9)M) for R5020 and was specific for progestins. The levels of receptor varied at different stages of mammary gland development; the levels were inversely proportional to the secretory activity of the gland. This negative corelation between receptors and secretion was further observed in studies in which lactational involution was induced experimentally. We propose that the functional significance of the modulation of progesterone receptors in normal mammary glands may be related to the known different effects of progesterone in this tissue.
Animals↗
Histopathogenesis of 7,12-diemthylbenz(a)anthracene-induced rat mammary tumors.
The histopathogenesis and growth behavior of mammary tumors and dysplasias induced by a single intragastric dose of 7,12-dimethylbenz[a]anthracene in 50-day-old virgin female Lewis rats were examined both in situ and after transplantation into gland-free mammary fat pads of syngeneic hosts. Terminal mammary ductules are indicated as a site of origin of both ovarian hormone-dependent mammary tumors and spontaneously gegressing mammary tumors, and terminal ductule hyperplasia appears to be an early stage in mammary tumor formation. The precancerous nature of hyperplastic alveolar nodules induced by dimethylbenzanthracene in rats has been further examined, and our studies indicate that these nodules are not significantly preneoplastic.
9,10-Dimethyl-1,2-benzanthracene↗
An empirical basis for the competition by dexamethasone to progesterone receptors as estimated with the synthetic progestin R5020.
Normal mammary glands of mice contain both progesterone and glucocorticoid receptors and the levels of both these receptors are modulated as a function of development. Measurement of progesterone receptors using the synthetic progestin, R5020, has led to conflicting data both with regard to the presence of progesterone receptor during certain developmental stages of the mammary gland and the ability of the glucocorticoids to compete for specific R5020 binding sites. In this report we have identified experimental conditions which allow for the separate measurements of the progesterone and glucocorticoid receptors in the same cytosol. If sulfhydryl reducing agents such as dithiothreitol are excluded from the assay buffer, R5020 binds to only a single class of high affinity sites in mammary cytosol of virgin mice and these binding sites exhibit a strict steroid specificity characteristic of progesterone receptors. In contrast, if dithiothreitol is included in the buffers, R5020 binds not only to the high affinity sites but also to certain saturable lower affinity sites; these lower affinity sites for R5020 also bind glucocorticoids such as dexamethasone. These findings should facilitate more accurate quantitation of both progesterone and glucocorticoid receptors in normal and neoplastic tissues and also be applicable to studies on the mechanism(s) of progesterone action.
Animals↗