TY - JOUR
T1 - Increased low density lipoprotein receptor expression mediated through the insulin-like growth factor-I receptor in cultured fibroblasts
AU - Ostlund, Richard E.
AU - Yang, Joseph W.
AU - Heath-Monnig, Ellen
AU - Semenkovich, Clay F.
PY - 1994/7
Y1 - 1994/7
N2 - Plasma insulin-like growth factor-I (IGF-I) levels are inversely correlated with apolipoprotein B and low density lipoprotein (LDL) cholesterol in humans. To identify a molecular basis for this observation, the effects of IGF-I on LDL receptor expression in fibroblasts were studied. IGF-I increased LDL receptors in cultured human skin fibroblasts at concentrations greater than 25 ng/ml. However, IGF-I effects were not easily quantitated due to secretion of inhibitory IGF-binding proteins by the cells. To circumvent this difficulty, QAYL, an IGF-I analog that binds to the IGF-I receptor but not to IGF-binding proteins, was used. QAYL increased LDL receptor number 56-72% with half-maximum effect at 0.6 ng/ml. α-IR3, a monoclonal antibody directed toward the IGF-I receptor, blocked this effect. QAYL treatment increased synthesis of LDL receptor protein without increasing LDL receptor mRNA levels or altering protein stability. Both QAYL and IGF-I increased LDL receptors prominently in cells that had been treated with physiological amounts of LDL cholesterol. IGF-I, acting through the IGF-I receptor and modulated by IGF-binding proteins, may contribute to the regulation of LDL metabolism by increasing translation of LDL receptor message.
AB - Plasma insulin-like growth factor-I (IGF-I) levels are inversely correlated with apolipoprotein B and low density lipoprotein (LDL) cholesterol in humans. To identify a molecular basis for this observation, the effects of IGF-I on LDL receptor expression in fibroblasts were studied. IGF-I increased LDL receptors in cultured human skin fibroblasts at concentrations greater than 25 ng/ml. However, IGF-I effects were not easily quantitated due to secretion of inhibitory IGF-binding proteins by the cells. To circumvent this difficulty, QAYL, an IGF-I analog that binds to the IGF-I receptor but not to IGF-binding proteins, was used. QAYL increased LDL receptor number 56-72% with half-maximum effect at 0.6 ng/ml. α-IR3, a monoclonal antibody directed toward the IGF-I receptor, blocked this effect. QAYL treatment increased synthesis of LDL receptor protein without increasing LDL receptor mRNA levels or altering protein stability. Both QAYL and IGF-I increased LDL receptors prominently in cells that had been treated with physiological amounts of LDL cholesterol. IGF-I, acting through the IGF-I receptor and modulated by IGF-binding proteins, may contribute to the regulation of LDL metabolism by increasing translation of LDL receptor message.
UR - http://www.scopus.com/inward/record.url?scp=0028304664&partnerID=8YFLogxK
U2 - 10.1210/me.8.7.904
DO - 10.1210/me.8.7.904
M3 - Article
C2 - 7527123
AN - SCOPUS:0028304664
VL - 8
SP - 904
EP - 909
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 7
ER -