Inhibitory effect of cyclosporin A on prolactin synthesis in GH3 cells.

Cyclosporin A (CsA), a potent immunosuppressant, is known to have various effects on the endocrine system, including the pituitary gland, the adrenal cortex, the testes, and the pancreatic islets. In this study, the effects of CsA on prolactin (PRL) synthesis and release were investigated in GH3 cells, a clonal strain of rat pituitary tumor. After incubation of confluent GH3 cells with various concentrations of CsA for 24 hr, the PRL content of the media decreased in a dose-dependent manner: by 28.5% with 100 ng/ml CsA (p < 0.01); and 45.8% with 2,000 ng/ml CsA (p < 0.001), compared with control. However, no significant change was observed in the intracellular PRL content. After removal of CsA from the medium, GH3 cells fully recovered normal secretory activity within 24-48 hr, thus indicating that the inhibitory effect of CsA on PRL secretion was reversible. Northern blot analysis revealed a decrease in the PRL mRNA level in cells treated with CsA. In conclusion, these data suggest that CsA inhibits PRL secretion by reducing the rate of biosynthesis. A possible site of action is on PRL gene expression at the level of mRNA transcription.