The regulatory function of spermidine in hormonal control of the development of mouse mammary gland in culture.

The interplay of insulin, glucocorticoid, and prolactin induces differentiation of mouse mammary gland in culture. Earlier studies indicated that spermidine plays a key role in hormonal control of mammary development by mediating some of the lactogenic actions of glucocorticoid. In this study we examined the effect of progesterone, an inhibitor of lactogenesis, on milk protein synthesis and spermidine accumulation. The maximal degree of inhibition, which was attained at 300 nM, was about 40% for casein synthesis, 90% for alpha-lactalbumin synthesis, and 70% for spermidine accumulation. The increase in the activity of S-adenosyl-L-methionine decarboxylase and spermidine synthetase, two key enzymes in polyamine biosynthesis, was inhibited by 55 and 65%, respectively, by progesterone. The extent of progesterone inhibition of milk protein synthesis was greatest in cultured tissue from virgin mice, which contained a low level of spermidine, whereas mammary explants from lactating mice, which contained a high level of spermidine, were insensitive to progesterone. The inhibitory effect of progesterone can be partially antagonized by cortisol, which causes an enhancement of spermidine accumulation. These results suggest that the synthesis and accumulation of spermidine serve as targets for the inhibitory action of progesterone on lactogenesis.