Cholera Toxin Treatment Increasesin VivoGrowth and Development of the Mouse Mammary Gland*

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Abstract
Daily sc injections of cholera toxin (CT; 0.1 .mu.g/day), a stimulator of adenylate cyclase activity, into intact female BALB/c mice for 20 days significantly (P < 0.05) increased mammary gland development scores from 2.0 .+-. 0.1 in controls to 3.6 .+-. 0.2 in CT-treated mice. Concurrent administration of 17.beta.-estradiol (E; 1.0 .mu.g/day) and progesterone (P; 1.0 mg/day) resulted in development scores of 4.1 .+-. 0.1 and 5.2 .+-. 0.1 in E/P and E/P + CT treatment groups, respectively (P < 0.05). If mice were ovariectomized before CT injection, the response to CT alone was abolished (development scores of 2.0 .+-. 0.1 and 1.9 .+-. 0.1 in controls and CT-treated mice, respectively). However, E/P restored the response to CT (scores of 3.2 .+-. 0.2 for E/P and 4.0 .+-. 0.1 for E/P + CT; P < 0.05) in ovariectomized mice. CT significantly (P < 0.05) increased mammary dry fat-free tissue weight from 2.89 .+-. 0.41 mg (controls) to 3.78 .+-. 0.37 mg (CT-treated) and from 4.03 .+-. 0.59 mg (E/P-treated) to 5.42 .+-. 0.91 mg (E/P + CT). Similary, CT treatment increased mammary DNA from 138.7 .+-. 11.7 .mu.g (controls) to 162.8 .+-. 14.4 .mu.g (CT) and from 178.5 .+-. 12.6 to 233.9 .+-. 28.0 .mu.g in the presence of E/P (P < 0.05). Furthermore, CT was found to be mammogenic in hypophysectomized mice treated with E (1.0 .mu.g/day), P (1.0 mg/day), deoxycorticosterone acetate (0.5 mg/day), T4 (0.2 .mu.g/ml drinking water), and glucose (50 mg/ml drinking water), i.e. mammary gland development scores were 1.5 .+-. 0.1 in mice treated with the above regimen and 3.1 .+-. 0.1 in mice treated with the above regimen plus CT for 14 days (P < 0.05). These results provided clear evidence, heretofore unreported, that systemic CT treatment increased mammary gland development and growth in femal mice. The mammogenic effects of CT are observed in intact female mice with or without exogenous E/P, in ovariectomized mice treated with E/P, and in hypophysectomized mice treated with E/P, deoxycortisone acetate, and T4.

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