Regulation of casein synthesis by polyamines in mammary gland explants of mice.
Studies were carried out to determine whether the actions of prolactin on the metabolism of the mammary gland may involve polyamines. In mouse mammary gland explants that were preincubated for 2 days with insulin plus hydrocortisone, the rate of [3H]leucine incorporation into casein was enhanced in a prolactin-like manner during a further incubation with spermidine plus cyclic GMP or phospholipase A. Putrescine (0.5 mM) plus PGF2alpha, cyclic GMP or arachidonic acid also enhanced the rate of casein synthesis: but PGF2alpha plus 0.5 mM arginine, ornithine or spermine had no effect. Methyl GAG, an inhibitor of the enzyme S-adenosyl-L-methionine decarboxylase (which is required for the conversion of putrescine to spermidine), abolished the putrescine plus PGF2alpha stimulation of casein synthesis. Since this drug did not affect the action of spermidine plus PGF2alpha on casein synthesis, the specific action of spermidine on casein synthesis is suggested. Neither arginine, ornithine nor the polyamines, by themselves, affected the rate of [3H]uridine incorporation into RNA or the rate of [3H]leucine incorporation into casein. Spermidine levels were elevated within 4 h after adding prolactin to explants which were preincubated for 2 days with insulin plus hydrocortisone; this effect was apparent during incubation periods of up to 48 h with prolactin. Arginase and ornithine decarboxylase activities were also elevated in response to prolactin. Arginase activity was only elevated, however, during long incubation periods with prolactin, i.e., during incubation periods of longer than 2 days. In contrast, ornithine decarboxylase activity was elevated by prolactin within a 30 min incubation period; this effect was maximal after 2 h and persisted during exposure periods of up to 24 h.
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002364:Caseins / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008935:Mitoguazone / Q000494:pharmacology; D009952:Ornithine / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010740:Phospholipases / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011388:Prolactin / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D011700:Putrescine / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D002364:Caseins; D007328:Insulin; D011073:Polyamines; D011460:Prostaglandins F; D013096:Spermine; D011388:Prolactin; D001120:Arginine; D000242:Cyclic AMP; D009952:Ornithine; D010740:Phospholipases; D009955:Ornithine Decarboxylase; D006152:Cyclic GMP; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine; D006854:Hydrocortisone