INSULIN-LIKE GROWTH-FACTORS - THEIR REGULATION OF GLUCOSE AND AMINO-ACID-TRANSPORT IN PLACENTAL TROPHOBLASTS ISOLATED FROM FIRST-TRIMESTER CHORIONIC VILLI

The transport of glucose and amino acids from the maternal to fetal ci rculation through the placenta is critical to the delivery of fuel for normal fetal growth and development. Little information indicates tha t transplacental glucose or amino acid transport is influenced by horm ones or polypeptide growth factors. We developed a continuous cell lin e of cytotrophoblastlike cells derived from first-trimester human chor ionic villi as a model system to study the regulation of glucose and a mino acid transport by insulinlike growth factors (IGFs). Using immuno cytochemical and biochemical criteria, the cells were shown to manifes t a trophoblastlike phenotype. The cells were maintained in serum-supp lemented medium until confluent, at which time they were shifted to se rum-free medium for one day. Experiments were initiated by transferrin g the cells to glucose-free assay buffer and incubating them with IGF- I, IGF-II or insulin. Glucose uptake was measured by the transport of 2-deoxy-D-[1,2-H-3]glucose (2[H-3]DG) in the presence or absence of cy tochalasin B, which has been shown to competitively inhibit glucose up take. IGF-I, IGF-II and insulin each enhanced 2[H-3]DG transport in a dose-dependent fashion. Amino acid transport was measured by incubatio n of the cells with IGF-I for 60 minutes, followed by a 5-minute chall enge with alpha-[methyl-H-3]aminoisobutyric acid. IGF-I mused a dose-d ependent increase in uptake of the amino acid analog. Radioreceptor as says using [I-125]insulinlike growth factor I ([I-125]IGF-I) demonstra ted that the trophoblast-derived cells contained high-affinity, satura ble receptors for IGF-I that also bound IGF-II. Insulin bound to this binding site with very low affinity. These data indicate that in contr ast to previous reports that glucose and amino acid transport in the p lacenta are unregulated processes, IGFs may exert local modulation of acute metabolic actions in trophoblast-derived cells via IGF-I recepto rs.