THE ROLE OF PROLACTIN AND GROWTH-HORMONE IN THE REGULATION OF CASEIN GENE-EXPRESSION AND MAMMARY CELL-SURVIVAL - RELATIONSHIPS TO MILK SYNTHESIS AND SECRETION

The have compared involution of the rat mammary gland, induced by litt er removal, where milk accumulation occurs, with involution induced in the presence of the suckling young by combined PRL and GH deficiency. Both treatments induced involutionary processes involving apoptosis, as judged by DNA ladders and resulted in significant decreases in the DNA content of the gland. Surprisingly, the effects of hormone depriva tion on protein output in milk were principally explained by the loss of secretory cells, as there were only modest decreases in casein mess enger RNA (mRNA) expression and protein synthesis rates per U DNA in v itro. The association of casein mRNA with the polysome fraction was al so unaffected by hormone deprivation, whereas involution induced by li tter removal resulted in much greater decreases in steady state levels of casein mRNA and an increased association of the mRNAs with the mon osome fraction. In PRL- and GPI-deficient rats, PRL treatment could pr event all of these effects, GH was partially effective, whereas putati ve mediators of GH action, insulin-like growth factor I (IGF-I), IGF-I I, and IGF-binding protein-3, were ineffective. This lack of effect of IGFs may be due to an inhibitory IGFBP, which we demonstrate to be pr esent in increased amounts in the involuting mammary gland.