Synthesis of α-fetoprotein and albumin by fetal mouse liver cultured in chemically defined medium

Abstract

Fetal mouse liver synthesizes two major secretory proteins: α-fetoprotein and albumin. The relative proportions of these proteins change during development. Fetal mouse liver secretes predominantly α-fetoprotein, and the neonatal mouse liver secretes predominantly albumin. α-Fetoprotein and albumin synthesis were studied in vitro using an organ culture system and a chemically defined medium (BGJ b). This medium does not support hepatocellular replication but maintains protein synthesis at high levels for prolonged periods of culture. Patterns of protein synthesis were analyzed as functions of gestational age and time in culture. The ratio of α-fetoprotein/albumin decreases from 1.4 on gestational Day 14 to 0.4 on gestational Day 18. However, when liver cultures were begun on any given gestational day, the ratio of α-fetoprotein/albumin remains constant for as long as 8 days in culture. Thus, developmental changes in α-fetoprotein and albumin synthesis are arrested under the conditions of this culture system. Fetal mouse liver secretes two electrophoretically distinguishable forms of albumin. One form is similar in mobility to albumin from adult mouse serum; the other more electropositive species is similar in mobility to proalbumin isolated from adult mouse liver microsomes and can be converted to albumin by mild trypsin treatment.