Bromocriptine-induced reversible lysosomal change and reduction of prolactin and growth hormone messenger RNA in cultured GH₃ cell lines

We examined the effects of bromocriptine on the ultrastructure and on the levelsof messenger RNA (mRNA) of prolactin and growth hormone (GH) in a cultured GH₃ cell line. Prolactin and GH concentrations measured by radioimmunoassay in the incubation medium as well as the cell number of the GH₃ cells were significantly decreased by treatment with 10^-4M bromocriptine for 24 hours. Electron microscopy of bromocriptine-treated GH₃ cells demonstrated accumulation of cytoplasmic vacuoles containing cytoplasmic components including secretory granules (crinophagy) which were positive for acid phosphatase staining. The remarkable morphological changes in GH₃ cells, induced by treatment with 10^-4M bromocriptine for 24 hours, disappeared 48 hours after substitution with bromocriptine-free medium. An immunoelectron-microscopic study demonstrated gold particles binding with antiprolactin antibodies not only In the cytoplasm but also inside vacuoles of GH₃ cells after incubation with bromocriptine for 24 hours. Treatment with 10^-4M bromocriptine for 24 hours caused the reduction both of mRNAs of prolactin measured by dot-blot hybridization and the Northern-blotting method and of GH measured by the Northern-blotting method. In conclusion, bromocriptine induces a reversible lysosomal change and could inhibit gene transcription of prolactin and GH in GH₃ cells.Endocr Pathol 4:28-33, 1993.