MAMMARY-GLAND DIFFERENTIATION IN HYPOPHYSECTOMIZED, PREGNANT MICE TREATED WITH CORTICOSTERONE AND THYROXINE

Swiss Webster mice were hypophysectomized or sham-operated on Day 11 of pregnancy. The animals were fitted s.c. with osmotic minipumps containing either corticosterone (B) dissolved in Molecusol (Pharmatec, Alachua, FL) or the vehicle alone immediately after they were hypophysectomized. Animals in some of die experimental groups also received thyroxine (T4) in their drinking water. The mice were killed on Day 18 of gestation, and mammary tissue was homogenized and extracted for assessment of DNA, RNA, alpha-lactalbumin, and alpha-casein. Serum was assayed for placental lactogen-I (PL-I), and placental lactogen-II (PL-II), B, and T4. The concentration of PL-II in serum was elevated in die hypophysectomized mice, whereas the PL-I concentration did not differ among experimental groups. Hypophysectomy decreased both T4 and B concentrations in serum, and administration of these hormones restored their serum concentrations to normal or, in some cases, somewhat higher than normal levels. Hypophysectomy reduced the total RNA content and RNA/DNA ratio of the mammary gland, but treatment with B alone or with B and T4 restored RNA levels to those of sham-operated animals. T4 alone was ineffective in restoring RNA levels. Sham-operated animals that received hormonal treatment (B and T4) had the highest levels of RNA in the mammary tissue. Hypophysectomized animals had reduced content and concentration of alpha-lactalbumin in die mammary gland as compared to all other experimental groups. Treatment with either B or T4 brought die levels of alpha-lactalbumin back up to that of sham-operated untreated animals, but highest content and concentration of alpha-lactalbumin were found in mammary glands of sham-operated and hypophysectomized mice treated with both B and T4. The levels of alpha-casein were not affected by hypophysectomy alone. However, concomitant high concentrations in serum of PL-II, resulting from hypophysectomy, and of B, resulting from an exogenous source, caused a significant increase in the mammary gland content and concentration of alpha-casein. In conclusion, prolactin and growth hormone are not essential for normal mammary differentiation during the latter half of pregnancy in the mouse, due to high circulating concentrations of PL-I and PL-II. This study also demonstrates that the hormonal control of the synthesis of alpha-lactalbumin and of alpha-casein differ in the mouse.