Enzymic differentiation in cultured fœtal hepatocytes of the rat: induction of serine dehydratase activity by dexamethasone and dibutyryl cyclic AMP

Serine dehydratase activity is absent from the rat foetal liver and normally appears in the immediate postnatal period. In foetal hepatocytes cultured from livers of various gestational ages, enzyme activity can be induced only in the simultaneous presence of dexamethasone and dibutyryl cyclic AMP in the culture medium. Adrenalin and glucagon can replace dibutyryl cyclic AMP. Actinomycin D and cordycepin both repress the response, a result that suggests the induction of enzyme synthesis involves the initial transcription of the enzyme gene(s). Inducibility is assessed in cultures prepared from foetuses aged between 15 and 19 days of gestation after 48 h of culture. No induction is obtained in cells from 15 day foetuses, only a marginal induction from 16 day foetuses, and a substantial induction from older foetuses. In cultures from older foetuses, 6-18 fold inductions are already demonstrable after 24 h of culture. While hepatocytes from more mature foetuses are able to acquire inductibility during culture, cells taken from 15 day foetuses do not develop in the same manner in spite of being maintained under identical conditions. These results suggest that a differentiation event occurs in vivo at about day 16 of foetal development which renders the hepatocyte inducible when cultured. Cells taken prior to this stage do not appear to acquire inducibility. This system represents a case of enzymic differentiation and requires the simultaneous presence of two inducer molecules. The mechanism of induction may represent a unique system in cellular differentiation.