Comparative studies on the regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) production by insulin and insulin-like growth factors in human hepatoma cells.
Production of insulin-like growth factor-binding protein-1 (IGFBP-1) by the liver is efficiently inhibited by insulin both in vivo and in vitro. Consequently, serum IGFBP-1 concentration reflects insulin bioactivity in portal vein. Sex hormone-binding globulin (SHBG) is another insulin-regulated liver-derived protein that has appeared promising in detecting individuals with portal hyperinsulinemia. We compared the regulation of IGFBP-1 and SHBG production by insulin and insulin-like growth factors (IGF-I and IGF-II) in human hepatoma cell cultures. Insulin equipotently inhibited IGFBP-1 and SHBG production, with maximal decrease in culture medium concentrations being about 35% for both proteins during 48 h of culture in serum-free medium. IGF-I and IGF-II also inhibited the IGFBP-1 and SHBG levels. We conclude that IGFBP-1 and SHBG are equally sensitive to ambient insulin concentrations in human hepatoma cell cultures, and the production of both proteins is also attenuated by the IGFs.
Kalme
T
T
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, FIN-00029 Huch, Finland. tarja.kalme@hus.fi
Koistinen
H
H
Loukovaara
M
M
Koistinen
R
R
Leinonen
P
P
D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D012738:Sex Hormone-Binding Globulin / Q000032:analysis / Q000096:biosynthesis*; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D012738:Sex Hormone-Binding Globulin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II