Insulin preincubation enhances insulin-like growth factor-II (IGF-II) action on steroidogenesis in human granulosa cells.
Although abundant mRNA for IGF-II has been detected in the human ovary, a role for IGF-II in steroidogenesis has not yet been established. In rat adipocytes, incubation with insulin greatly increases cell-surface IGF-II receptor (5-fold) and the receptor is rapidly internalised in the absence of insulin. We have therefore investigated the effects of insulin preincubation on the response of granulosa cells from unstimulated ovaries to a range of doses of IGF-II. In the absence of insulin, IGF-II stimulated steroidogenesis in only one of three experiments. After incubation with 10 ng/ml insulin, there was a dose-dependent response to IGF-II in all experiments. Cells incubated with insulin produced 5-10 fold more estradiol in response to IGF-II than those incubated without. In contrast, insulin produced only a small increase of estradiol in response to IGF-I. These results demonstrate a synergistic interaction of insulin with IGF-II in human granulosa cells and suggest that there is an important role for IGF-II in human ovarian steroidogenesis.
Mason
H D
HD
Department of Obstetrics and Gynaecology, St. Mary's Hospital Medical School, Imperial College, London, UK.
Willis
D S
DS
Holly
J M
JM
Franks
S
S
D000328:Adult; D002478:Cells, Cultured; D004357:Drug Synergism; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*
D007328:Insulin; D011374:Progesterone; D004958:Estradiol; D007335:Insulin-Like Growth Factor II