An insulin-like growth factor-binding protein in ovarian follicular fluid blocks follicle-stimulating hormone-stimulated steroid production by ovarian granulosa cells.
An inhibitor of FSH action on granulosa cells has been purified from porcine follicular fluid using a combination of ammonium sulfate precipitation, dialysis in 30% (vol/vol) acetic acid, gel filtration chromatography under acidic conditions, and several steps of reverse phase HPLC. Activity was monitored by using an in vitro granulosa cell bioassay, measuring the effect of the inhibitor on FSH-stimulated estradiol production. The purified polypeptide dose-dependently inhibited production of both estradiol (EC50 = 0.7 nM) and progesterone (EC50 = 1.3 nM) by rat granulosa cells cultured in the presence of 20 ng/ml FSH. N-Terminal sequence analysis revealed a high degree of homology with the 53,000 mol wt human GH-dependent insulin-like growth factor-binding protein (IGF-BP). Coincubation of stoichiometric amounts of IGF-I or -II and the inhibitor (IGF-BP) resulted in complete neutralization of the inhibitory effect. Since both IGFs are produced locally in the ovary and exert stimulatory effects on granulosa cells, local production of IGF-BP may provide an important means of regulating ovarian follicle growth.
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Department of Molecular Endocrinology, Whittier Institute, La Jolla, California 92037.
Shimonaka
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Shimasaki
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Ling
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D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008970:Molecular Weight; D010455:Peptides / Q000032:analysis* / Q000494:pharmacology; D051381:Rats
D000596:Amino Acids; D002352:Carrier Proteins; D004967:Estrogens; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C018355:intraovarian peptides; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone