COORDINATE TRANSCRIPTIONAL REGULATION OF THE 3 FIBRINOGEN SUBUNIT GENES BY GLUCOCORTICOIDS IN CULTURED PRIMARY LIVER-CELLS FROM XENOPUS-LAEVIS

Xenopus laevis primary hepatocytes in culture are induced by glucocort icoid hormones to synthesize and secrete fibrinogen. The increase in p roduction of the protein is preceded by a 10- to 30-fold elevation of the mRNAs coding for the three fibrinogen subunits, Aalpha, Bbeta, and gamma. To analyze the mechanisms underlying this coordinate control o f independent genes in a common regulatory network, we show here that the steroid hormone induced simultaneous activation of transcription o f the three fibrinogen subunit genes. Using an optimized transcription run-on assay for nuclei from Xenopus primary liver cells, we demonstr ate that glucocorticoids rapidly stimulated transcription of the Aalph a fibrinogen subunit gene by 15- to 20-fold, the Bbeta gene by 5- to 1 0-fold, and the gamma gene by 5- to 15-fold. The three genes exhibited a highly concerted response to the hormone, in which maximal stimulat ion occurred by 30 min and was maintained for at least 16 h. Blocking new protein synthesis before hormone treatment reduced total transcrip tion by 45% and partially inhibited specific hormonal induction of all three fibrinogen subunit genes. The effect of glucocorticoids on fibr inogen transcription, therefore, was dependent in part on ongoing prot ein synthesis, suggesting that hormonal stimulation uses already synth esized stable factors, but also requires labile or newly synthesized f actors for the full effect.