Insulin-like growth factor I (IGF-I) synergistically amplified the stimulatory effect of low density lipoprotein (LDL) on progesterone biosynthesis by primary cultures of swine ovarian cells. The mechanisms subserving this facilitative interaction included the following. 1) IGF-I's synergism with LDL was associated with a decrease in the mean half-maximally stimulatory concentration of LDL from 20â€“3.5 Î¼g/ml. 2) IGF-I increased by 3- to 6-fold the number of specific high affinity LDL receptors on ovarian cells, with no change in apparent binding affinity. 3) IGF-I augmented by 3- and 18-fold the maximal rates of [125I]iodo-LDL internalization and degradation, respectively, without altering half-maximally effective concentrations of LDL supporting these processes. 4) IGF-I increased by 2- to 2.5-fold the total mass of free and esterified cholesterol contained in granulosa cells. 5) IGF-I stimulated the intracellular accumulation of free [3H]cholesterol and [3H]cholesteryl ester from exogenous [3H]cholesteryl linoleate-labeled LDL, and amplified [3H] progesterone secretion by granulosa cells exposed to this source of lipoprotein-borne sterol. 6) These actions of IGF-I were demonstrated at 30- to 100-fold lower concentrations of IGF-I than insulin. We conclude that IGF-I and LDL synergistically enhance progesterone biosynthesis by ovarian cells. This synergism occurs in part via mechanisms that regulate the effectual delivery of lipoprotein-borne cholesterol substrate into cellular sterol pools that participate in steroid hormone biosynthesis.
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