COORDINATE REGULATION OF FIBRINOGEN SUBUNIT MESSENGER-RNA LEVELS BY GLUCOCORTICOIDS IN PRIMARY CULTURES OF XENOPUS LIVER PARENCHYMAL-CELLS

Fibrinogen synthesis is specifically induced by a synthetic glucocorticoid, dexamethasone, in primary liver parenchymal cell cultures of the frog Xenopus laevis. Here we demonstrate that this increase in the level of fibrinogen protein production is accompanied by an induction in the three mRNAs coding for the fibrinogen subunits, designated A-alpha, B-beta, and gamma. The stimulation of fibrinogen mRNA levels appears to be mediated by the glucocorticoid receptor, because 1) the dose-response relationship parallels the reported affinity of dexamethasone for the Xenopus glucocorticoid receptor; and 2) the induction is blocked by RU 486, a potent antiglucocorticoid. All three subunit mRNA levels are induced coordinately by the hormone. The response is characterized by a detectable increase as early as 2-4 h after dexamethasone addition, continuing to a final 10- to 30-fold increase over basal levels by 60 h. The induction is specific for the fibrinogen mRNAs; total cellular RNA content and the levels of other mRNAs are unaffected by the hormone. Dexamethasone-mediated stimulation of A-alpha and B-beta mRNA production occurs in the absence of protein synthesis, whereas increased production of gamma mRNA is completely blocked under the same conditions. Thus, the A-alpha and B-beta genes are probably regulated at least in part by direct transcriptional activation by glucocorticoid-receptor complexes. Induction of the gamma gene is dependent on newly synthesized or labile proteins, which could be required for either transcription or posttranscriptional processes. These data suggest that different proteins are involved in regulation of the three fibrinogen genes.