SYNERGISM OF ESTROGEN AND PROGESTERONE ON MAMMARY GLAND GROWTH IN GUINEA PIGS1

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Abstract
Guinea pigs were treated for varying periods of time with a range of doses of estradiol benzoate and/or progesterone. Typically, the steroids were injected subcutaneously in separate sites three times a week for four or eight weeks. Growth was assessed histologically in all experiments. In animals given combinations of estrogen and progesterone, measurements of nucleic acids, total nitrogen, per cent dry and defatted-dry weight, and slice respiration of mammary tissue supplemented the histological approach. The amount of lobulo-alveola growth attained with estrogen alone depended upon both the dosage and length of treatment. Glands from males showed less growth after estrogen than those from females, while those from intact females were larger than those from castrated females. No dose of estrogen was found when elicited ductal proliferation without at the same time causing some lobular growth, but the dose was limited so that the synergistic action of progesterone could be demonstrated. Progesterone alone induced no growth, but when added to the estrogen treatments, enhanced lobulo-alveolar growth. Augmentation of parenchymal growth was paralleled by increases in percentage dry weight, and especially percentage defatted-dry weight of the organ. Total mammary weight proved an inaccurate index of hormonal stimulation. Combinations of estrogen and progesterone brought about growth of mammary glands with greater concentrations of DNA and RNA, increased respiration, and slightly greater concentrations of total nitrogen than obtained with estrogen alone. The concentration of these constituents and respiratory activity was also dependent upon the doses of the hormones. Mammary glands developed experimentally showed lower concentrations of nucleic acids and less respiratory activity than those of late pregnancy. The results are believed to show that progesterone synergizes with estrogen in eliciting lobulo-alveolar growth of the mammary glands in guinea pigs in a manner similar to that established for other species, in spite of earlier negative reports.