The insulin-like growth factor, somatomedin-C, modulates low density lipoprotein metabolism by swine granulosa cells.
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. IGF-I's synergism with LDL was associated with a decrease in the mean half-maximally stimulatory concentration of LDL from 20-3.5 micrograms/ml. 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. 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. IGF-I increased by 2- to 2.5-fold the total mass of free and esterified cholesterol contained in granulosa cells. 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. 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.
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology*; D013552:Swine
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D013002:Somatomedins; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol