Regulation of growth hormone-independent insulin-like growth factor-binding protein (BP-28) in cultured human fetal liver explants

• Published in: The journal of clinical endocrinology and metabolism Vol. 69; no. 2; p. 246
• Main Authors: Lewitt, M S, Baxter, R C
• Format: Journal Article
• Language: English
• Published: United States 01.08.1989
• Subjects: Amniotic Fluid - analysis; Carrier Proteins - biosynthesis; Colforsin - pharmacology; Culture Techniques; Cycloheximide - pharmacology; Dexamethasone - pharmacology; Fetus - metabolism; Glucagon - pharmacology; Glucose - pharmacology; Humans; Immunochemistry; Insulin - pharmacology; Insulin-Like Growth Factor Binding Proteins; Liver - drug effects; Liver - embryology; Liver - metabolism; Theophylline - pharmacology
• ISSN: 0021-972X
• DOI: 10.1210/jcem-69-2-246

Cultured human fetal liver explants were used to study regulation of the GH-independent insulin-like growth factor-binding protein (BP-28). BP-28 was produced by fetal liver explants at approximately 200 ng/mg total tissue protein.day between days 3 and 6 in culture and was inhibited 60% after 3-day exposure to cycloheximide (10 micrograms/mL). BP-28 production was stimulated over 3-fold by 20 mmol/L theophylline, over 2-fold by 30 mumol/L forskolin, and 90% by 10 micrograms/mL glucagon. The glucose concentration in the medium inversely regulated BP-28 production, which was 68% higher in 2 mmol/L glucose than in 30 mmol/L glucose (P less than 0.001); in contrast, albumin production was 40% lower in 2 mmol/L glucose than in 30 mmol/L (P less than 0.05). BP-28 levels were inhibited 50% by 300 nmol/L insulin or 3 mumol/L dexamethasone. In acid extracts of cultured tissue, BP-28 levels were less than 10% of the amount secreted in 48 h. These results are consistent with the conclusion that intracellular glucose availability is an important regulator of hepatic BP-28 synthesis.