Insulinlike 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 circulation through the placenta is critical to the delivery of fuel for normal fetal growth and development. Little information indicates that transplacental glucose or amino acid transport is influenced by hormones or polypeptide growth factors. We developed a continuous cell line of cytotrophoblastlike cells derived from first-trimester human chorionic villi as a model system to study the regulation of glucose and amino acid transport by insulinlike growth factors (IGFs). Using immunocytochemical and biochemical criteria, the cells were shown to manifest a trophoblastlike phenotype. The cells were maintained in serum-supplemented medium until confluent, at which time they were shifted to serum-free medium for one day. Experiments were initiated by transferring 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-[1,2-3H]glucose (2[3H]DG) in the presence or absence of cytochalasin B, which has been shown to competitively inhibit glucose uptake. IGF-I, IGF-II and insulin each enhanced 2[3H]DG transport in a dose-dependent fashion. Amino acid transport was measured by incubation of the cells with IGF-I for 60 minutes, followed by a 5-minute challenge with alpha-[methyl-3H]aminoisobutyric acid. IGF-I caused a dose-dependent increase in uptake of the amino acid analog. Radioreceptor assays using [125I]insulinlike growth factor I ([125I]IGF-I) demonstrated that the trophoblast-derived cells contained high-affinity, saturable receptors for IGF-I that also bound IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)
Kniss
D A
DA
Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus 43210-1228.
Shubert
P J
PJ
Zimmerman
P D
PD
Landon
M B
MB
Gabbe
S G
SG
D000596:Amino Acids / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000502:physiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism*
D000596:Amino Acids; D007328:Insulin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D005947:Glucose