STUDIES ON THE MECHANISM BY WHICH PROLACTIN STIMULATES ALPHA-AMINOISOBUTYRIC-ACID UPTAKE INTO CULTURED MOUSE MAMMARY TISSUES

Studies were carried out to determine the possible roles of the polyam ines, cyclic nucleotides, icosanoid products, and protein kinase C in the prolactin regulation of amino acid transport in cultured mammary g land explants derived from 12-14 day pregnant mice. Elevated cyclic AM P concentrations impaired the PRL stimulation of AIB transport. DBcAMP as well as the phosphodiesterase inhibitors theophylline and methyl i sobutyl-xanthine, when added to the cultures, attenuated or abolished the PRL responses. 8-Bromo cyclic GMP elicited a modest stimulation of AIB transport. Ongoing polyamine synthesis appears to be necessary fo r PRL to effect a stimulation of AIB transport since methylglyoxal bis (guanyl hydrazone), an inhibitor of S-adenosyl methionine decarboxylas e, abolishes the PRL response; specificity of this effect was establis hed by its reversal with the addition of spermidine to the culture med ium. Ongoing icosanoid product synthesis also appears to be required f or the PRL stimulation of AIB transport since indomethacin abolishes t he PRL response. Finally, the inhibition of the PRL response by the pr otein kinase C inhibitor H-7 suggests that the activation of kinase C activity may also be involved in the PRL stimulation of AIB transport.