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. I n rat adipocytes, incubation with insulin greatly increases cell-surfa ce IGF-II receptor (5-fold) and the receptor is rapidly internalised i n the absence of insulin. We have therefore investigated the effects o f insulin preincubation on the response of granulosa cells from unstim ulated ovaries to a range of doses of IGF-II. In the absence of insuli n, IGF-II stimulated steroidogenesis in only one of three experiments. After incubation with 10ng/ml insulin, there was a dose-dependent res ponse to IGF-II in all experiments. Cells incubated with insulin produ ced 5-10 fold more estradiol in response to IGF-II than those incubate d without. In contrast, insulin produced only a small increase of estr adiol in response to IGF-I. These results demonstrate a synergistic in teraction of insulin with IGF-II in human granulosa cells and suggest that there is an important role for IGF-II in human ovarian steroidoge nesis.