The differential actions of cortisol on the accumulation of α-lactalbumin and casein in midpregnant mouse mammary gland in culture

Abstract

The dose-response relationship between cortisol and the accumulation of the two milk proteins, casein and α-lactalbumin, was studied in organ culture of mammary gland from midpregnant mice. The accumulation of casein was low in culture with insulin but was enhanced by the further addition of prolactin. Further increases in casein were effected by the addition of cortisol in increasing concentrations up to 3 × 10 −6 M, which was optimal for the accumulation of this protein. The content of α-lactalbumin in explants was similarly low in culture with insulin alone, but, in contrast, was increased to a maximal level by the addition of insulin and prolactin. The addition of cortisol up to 3 × 10 −8 M with insulin and prolactin did not further increase the level of α-lactalbumin; in fact, at concentrations above 3 × 10 −7 M the steroid caused progressive inhibition of the accumulation of this protein in cultured explants. Studies of the appearance of casein and α-lactalbumin in incubation medium during organ culture revealed the presence of substantial amounts of these milk proteins. During the first 2 days of culture with insulin, prolactin and 3 × 10 −6 M cortisol, the amount of α-lactalbumin in culture medium was almost equal to the level found in tissue, whereas in the presence of 3 × 10 −8 M cortisol, or in the absence of exogenous steroid, over 70% of total α-lactalbumin was retained in tissue. The observed difference in the amount of α-lactalbumin in culture medium can, however, only partially account for the inhibitory effect of high doses of cortisol on the accumulation of α-lactalbumin in cultured mammary explants. In contrast to α-lactalbumin, the relative amount of casein in culture medium containing insulin and prolactin was smaller—19% of total casein synthesized—and was further reduced to 16% and 11% of the total in the presence of 3 × 10 −8 M and 3 × 10 −6 M cortisol, respectively. The above results indicate that cortisol exerts dose-dependent differential actions on the accumulation of casein and α-lactalbumin in mouse mammary epithelium in vitro.