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 pituit ary (AP) cells, and may serve as a paracrine inhibitor of PRL release. The present studies investigated effects of CT on basal and TRH-induc ed PRL mRNA levels in rat AP and rat pituitary tumor GH(3) cells. CT a ttenuated steady-state PRL mRNA levels in a dose-dependent fashion in primary rat AP and GH(3) cells. The kinetics of CT action suggests tha t 100 nM 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 decrea sed the rate of PRL gene transcription by 80% after 30 min of incubati on. CT did not affect PRL mRNA levels in Ca2+-depleted GH(3) cells but dramatically decreased them in Ca2+-repleted cells. Bay K 8644 induce d increase in PRL mRNA levels of Ca2+-repleted GH(3) cells and CT did not affect this increase. These results suggest that CT rapidly and se lectively inhibits PRL gene transcription in primary AP and GH(3) cell s, and support a possibility that CT-induced attenuation of PRL mRNA m ay involve cytoplasmic Ca2+.