Calcitonin inhibits prolactin gene transcription in rat pituitary cells

Our recent studies have shown that calcitonin (CT)-like immunoreactive peptide is synthesized and released from cultured rat anterior pituitary (AP) cells, and may serve as a paracrine inhibitor of PRL release. The present studies investigated effects of CT on basal and TRH-induced PRL mRNA levels in rat AP and rat pituitary tumor GH(3) cells. CT attenuated steady-state PRL mRNA levels in a dose-dependent fashion in primary rat AP and GH(3) cells. The kinetics of CT action suggests that 100NM: CT caused a significant decline after 3 h, and the inhibition was sustained at least until the longest tested incubation period of 30 h. Results from nuclear run-on assays suggest that 100 nM CT decreased the rate of PRL gene transcription by 80% after 30 min of incubation. CT did not affect PRL mRNA levels in Ca(2+)-depleted GH(3) cells but dramatically decreased them in Ca(2+)-repleted cells. Bay K 8644 induced increase in PRL mRNA levels of Ca(2+)-repleted GH(3) cells and CT did not affect this increase. These results suggest that CT rapidly and selectively inhibits PRL gene transcription in primary AP and GH(3) cells, and support a possibility that CT-induced attenuation of PRL mRNA may involve cytoplasmic Ca(2+).