Glucocorticoid-dependent expression of the albumin gene in adult rat hepatocytes.

In primary cultures of adult rat hepatocytes, transcription of the albumin gene, measured as incorporation of [alpha-32P]UTP into mRNA in isolated nuclei, decreased dramatically during culture without addition of serum and hormone, becoming almost negligible 10 h after plating. Of the hormones tested, dexamethasone (0.1 microM) prevented this decrease and restored the transcription within 2 h to the same level as that before culture. The half-maximum dose of dexamethasone for induction of transcription of the albumin gene was about 30 nM. The in vitro finding that expression of the albumin gene is strictly regulated by glucocorticoid was confirmed by an in vivo experiment in adrenalectomized rats showing that the transcription decreased markedly 14 days after adrenalectomy, but was restored rapidly by administration of hydrocortisone. This finding was also supported by identification of a glucocorticoid regulatory sequence from -50 to -62 base pairs between the TATA box and CAT box upstream of the 5'-end of the albumin gene. Cycloheximide inhibited the induction of transcription of the albumin gene by dexamethasone, suggesting that a rapidly induced mediator protein, which is also regulated by glucocorticoid, is involved in the induction of albumin gene expression by glucocorticoid. The albumin gene was also regulated by various other hormones besides glucocorticoid. Glucagon markedly enhanced the transcription induced by dexamethasone, although glucagon alone had no effect. Conversely, epinephrine suppressed stimulation of expression of the albumin gene by dexamethasone. Insulin and triiodothyronine had no effect on transcription of the albumin gene. From these findings we conclude that expression of the albumin gene depends strictly on glucocorticoid, and this dependence is modulated by other hormones.