Hormonal regulation of casein messenger RNA (mRNA).

Lactogenesis in mammary gland of the mouse requires cortisol (or corticosterone) and prolactin. In this paper we review some recent findings in our laboratory regarding influence of the corticosteroid on casein mRNA activity of lactating mammary gland. Adrenal ablation in nursing mothers results in loss of larger ribosomal aggregates (polysomes) from mammary cells; and this is accompanied by virtual abolition of immunologically detectable casein synthesis activity of the polysomes. Immunologically determined casein mRNA activity in phenol-chloroform-extracted lactating mammary cell RNA was assayed in ascites tumor cell ribosome cell-free protein synthesis system. Adrenalectomy induces 90% loss of casein mRNA activity of mammary cells of nursing mothers; this adverse response is also preventable by cortisol therapy of the animal. This suggests that the glucocorticoid influences the concentration of functionally active casein mRNA in the mammary cells. Cortisol treatment of adrenalectomized mothers also causes a pronounced increase of precursor ([H]uridine) incorporation into both rRNA and poly(A) mRNA. The latter includes mRNA species having a sedimentation value lower than 18S rRNA. Isolated nuclei of lactating mammary cells were assayed in an in vitro RNA polymerase system. RNA synthesized by the isolated nuclei in vitro after analysis on Sigmacell revealed that it includes poly(A) mRNA. This finding improves the feasibility of monitoring the influence of the glucocorticoid on mRNA transcriptional activity by the mammary chromatin. In addition results are presented to show that casein mRNA is inducible in the mammary cells in organ culture of the whole mammary gland in medium containing insulin, prolactin and cortisol. The significance of these findings concerning elucidation of the molecular mechanisms of synergism between the glucocorticoid and prolactin on modulation of the milk protein mRNA, and hence the developmental biology of the mammary gland, is discussed. [ABSTRACT FROM AUTHOR]