Cyclic nucleotides and the control of epithelial cell proliferation: cyclic CMP may be a partial mediator of the response of the pigeon crop-sac to prolactin.

Abstract

The possible role of cyclic nucleotides as second messengers mediating hormone-induced cellular growth in vivo was investigated using the proliferative response of the pigeon crop-sac mucosal epithelium to prolactin (PRL) as a model system. Local injections of cAMP, cCMP, cGMP, cTMP or cUMP alone over the prolactin-responsive cells had no mitogenic effect. When injected along with a small dose of PRL, cAMP at doses above 1 micromole inhibited the response by 10%. While cGMP at a dose of 10 micromoles augmented the response by 47%. In fact, cCMP gave a log-linear dose-response relationship with significant augmentation of the response to PRL observed with doses as low as 0.01 micromole. Cyclic UMP, cTMP and various 5'-nucleotide monophosphates had no effect on the response to the hormone. When the dibutyryl analogs of the cyclic nucleotides were tested for their ability to potentiate the response to PRL, only dibutyryl cCMP was effective. These data suggest that cCMP may be a partial mediator of the proliferative action of PRL in this system, but it is probably not the sole second messenger for prolactin's action in these cells. Our results also indicate that failure of a cyclic nucleotide to mimic a hormone-induced response by itself does not prove that the compound is uninvolved in the hormones's action.