Effects of estrogen and dexamethasone on a transgenic pituitary cell line : regulation of hormone and chromogranin/secretogranin expression

BACKGROUND: Recent studies with the growth hormone releasing hormone (GHRH) transgenic mouse model have shown that growth hormone (GH) and prolactin (PRL) cell hyperplasia and adenomas develop in a time-dependent manner after chronic stimulation by GHRH. However, the adenomatous foci have not been shown to be neoplastic with the ability to proliferate in vitro in the absence of GHRH stimulation. EXPERIMENTAL DESIGN: A cell line was established from an enlarged pituitary from a GHRH transgenic mouse. The cells proliferated readily in culture and were characterized with respect to PRL and GH production and response to estradiol and dexamethasone. The production of chromogranin/secretogranin (Cg/Sg) mRNA transcripts and the regulation of Cg/Sg expression was also analyzed in the newly established cell line to analyze the relationship between PRL, GH, and Cg/Sg production by this cell line. RESULTS: The tumor cells responded to 10(-7) M 17 beta-estradiol (estradiol) by increasing the percentage of immunoreactive PRL-positive cells, and to dexamethasone by decreasing the percentage of PRL-positive cells and mRNA levels. Dexamethasone (10(-7) M) treatment resulted in a 3-fold reduction in PRL mRNA and CgB mRNA, whereas GH and Sg II mRNAs were both increased after dexamethasone treatment. CgA mRNA level was not changed significantly by estradiol or dexamethasone in this cell line. CONCLUSIONS: This stable transgenic cell line is regulated by estradiol and dexamethasone with changes in PRL, GH, and Cg/Sg mRNA transcript levels. There is concordant regulation of PRL and CgB mRNAs as well as GH and SgII mRNAs. These findings indicate that this cell line can be used to study the regulation and possible functions of Cg/Sg in vitro.