Inhibitory effects of insulin-like growth factor-binding proteins on steroidogenesis by human granulosa cells in culture.
The effects of insulin-like growth factor-binding proteins (IGFBPs) 1 and 3 on steroidogenesis by human granulosa cells has been examined. Both IGFBP-1 and IGFBP-3 produced a dose-related inhibition of IGF-I-stimulated oestradiol accumulation in granulosa cell-conditioned medium with complete reversal of the effects of IGF-I in the presence of a molar excess of binding protein. IGFBPs 1 and 3 also exerted a small (25-40%) but significant and consistent inhibition of oestradiol secretion in response to follicle-stimulating hormone (FSH) alone. The progesterone response to IGF-I was inhibited by IGFBPs 1 and 3 but there was no effect on FSH-stimulated progesterone production. These data support the concept of a physiologically important intraovarian IGF system in the human ovary and demonstrate an unequivocally inhibitory effect of IGFBPs 1 and 3 on IGF-I-stimulated granulosa cell steroidogenesis.
Mason
H D
HD
Department of Obstetrics and Gynaecology, Imperial College of Science, Technology and Medicine, St Mary's Hospital Medical School, London, UK.
Willis
D
D
Holly
J M
JM
Cwyfan-Hughes
S C
SC
Seppala
M
M
Franks
S
S
D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone