Cyclic nucleotides and polyamines in prolactin stimulation of lactose biosynthesis

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The possible roles of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) and of polyamines on the early effect of prolactin (PRL) on lactose biosynthesis have been investigated in cultured mammary gland explants derived from mice 12-14 days pregnant. Elevated cAMP concentrations impaired the PRL stimulation of [3H]glucose incorporation into lactose. Adding dibutyryl cAMP (0.1-0.5 mM) or phosphodiesterase inhibitors [methyl isobutylxanthine (0.1-0.5 mM) or theophylline (0.5-5.0 mM)] to the culture medium abolished the PRL response. The addition of 8-bromo cGMP (0.5 mM) with or without 1.0 mM spermidine had no effect on the PRL stimulation of lactose synthesis. By itself, 1.0 mM spermidine consistently produces a small but significant PRL-like stimulation of lactose synthesis in this system. Ongoing polyamine metabolism appears to be necessary for the PRL effect on lactose synthesis because 100 microM methylglyoxal bis(guanyl hydrazone), an inhibitor of S-adenosyl methionine decarboxylase, abolished the PRL response. alpha-Difluoromethylornithine, an inhibitor of ornithine decarboxylase activity, at concentrations from 1.0 to 10 mM had no effect on the PRL stimulation of lactose synthesis.