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.
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, FIN-00029 Huch, Finland. tarja.kalme@hus.fi
T
T
Kalme
H
H
Koistinen
M
M
Loukovaara
R
R
Koistinen
P
P
Leinonen
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