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Normal human adult resting mammary gland explants were cultured during 7 days. The influence of hormones on DNA synthesis was assessed by autoradiography after incubation with tritiated-thymidine. Estriol was added to the medium at 3 different concentrations. With 0.01 ng/ml the labeling index remained at the level observed in the controls in the basic unenriched medium. A 10- and 100-fold increase of estriol elicited a transient, significant and dose-related increase of DNA synthesis on the 2nd day of organ culture. Estriol gave a qualitatively different profile of DNA synthesis than estradiol at 1.0 ng/ml. The results are compared with the effect of progesterone.

The direct influence of the three basic natural estrogens, estrone, 17 beta-estradiol and estriol, on DNA synthesis in human normal mammary epithelial cells was investigated in organ culture during 7 days, and was assessed by autoradiography. A threshold concentration of I.O. ng per ml was needed to elicit a significant stimulation by estradiol and estriol. No significant increase in the incorporation of tritiated-thymidine could be obtained with estrone in the same conditions. These observations are in keeping with the hypothesis put forward by Gurpide, Tseng and Gusberg (1977) that estrone per se might be devoid of any direct estrogenic effect.

Adenosine triphosphatase enzymatic activity was investigated in human approximatively normal, dysplastic and neoplastic mammary tissue, by three different methods. Staining intensity varied within wide limits; myoepithelial cells and blood vessels showed similar enzymatic activity. Epithelial cells reacted only faintly, or not at all; carcinoma cells were never labelled. Stromal response was highly variable. The calcium-cobalt method of Padykula and Herman gave more intense reactions than the lead-nitrate procedure of Wachstein and Meisel, either in the original form or according to the modifications recommended by Russo and Wells. With the latter method the sharpness of stain deposits on the different structures was markedly enhanced. The functional significance of ATPase activity is discussed.

Nonspecific alkaline phosphatase activity was identified in human normal and diseased breasts with the use of the calcium-cobalt, the lead-nitrate, and the azo-dye methods. The results varied not only with the staining method, but also with the functional status of the breast structures. In normal, dysplastic, and fibroadenomatous tissues there was a strong parallelism between myoepithelial and capillary enzyme activities. The calcium-cobalt method was the only technique which allowed staining of carcinoma cells; cancer stromal enzyme activity was evidenced only with the use of the same method. Our findings suggest that nonspecific alkaline phosphatase activity probably reflects a functional status of the labelled structures; the enzyme activity of myoepithelial cells is variable and not really specific.

A morphometric study of normal and sub-normal adult human mammary tissue is presented. The semi-quantitative analysis showed an increased number of lobules in sub-normal glands versus normal ones. Minor alterations, consistent with the classical concept of incipient fibrocystic disease were found in both. Quantitative morphometry (Multiple Purpose Test) confirmed the first, rather subjective, impression that the section surface occupied by lobules was nearly three times larger in sub-normal glands. This finding was due to an higher number of more extended lobules per surface unit. The extra-lobular ducts in sub-normal tissues appeared larger, but their number per surface unit was not significantly increased when compared to normal specimens. Variations between individuals, even as variations in the same gland were wide. It is suggested that "adenosis" is an age-related phenomenon and that fibrosis and cystic dilatation may be a normal manifestation of ageing of the breast. A reevaluation of the concept of true mammary dysplasia might be needed.