title: Insulin-like growth factor-I (IGF-I) inhibits production of IGF-binding protein-1 while stimulating estradiol secretion in granulosa cells from normal and polycystic human ovaries.
abstract: We have investigated the actions of FSH and insulin-like growth factor-I (IGF-I) on the production of IGF-binding protein-1 (IGFBP-1) by granulosa cells from unstimulated normal and polycystic (PCO) human ovaries and related these effects to those on estradiol (E2). IGFBP-1 concentrations were measured in granulosa cell-conditioned medium (48-h culture with 10(-7) M testosterone) and follicular fluid. IGF-I (50 ng/mL), in the absence of FSH, stimulated E2 production by granulosa cells from both normal and polycystic ovaries, and there was a synergistic action between IGF-I and FSH. Granulosa cells secreted IGFBP-1 in concentrations ranging from 20-500 pg/1000 cells.48 h, with cells from two of four normal and three of four polycystic ovaries showing a dose-related increase in IGFBP-1 production in response to FSH. In contrast, the addition of as little as 100 pg/mL IGF-I to cells incubated with testosterone or testosterone plus FSH, caused complete inhibition of IGFBP-1 production. FSH treatment produced the expected dose-related increase in E2 accumulation. IGFBP-1 was detectable in fluid from all sizes of follicle tested, but there was no correlation of IGFBP-1 concentrations with follicle size and no difference between normal and polycystic ovaries. These data indicate that IGFBP-1 and E2 are differentially regulated by IGF-1 in the human ovary.
authors.affiliation: Department of Obstetrics and Gynecology, St. Mary's Hospital Medical School, Imperial College of Science Technology and Medicine London, United Kingdom.
authors.forename: H D
authors.initials: HD
authors.lastname: Mason
authors.forename: R
authors.initials: R
authors.lastname: Margara
authors.forename: R M
authors.initials: RM
authors.lastname: Winston
authors.forename: M
authors.initials: M
authors.lastname: Seppala
authors.forename: R
authors.initials: R
authors.lastname: Koistinen
authors.forename: S
authors.initials: S
authors.lastname: Franks
mesh_terms: D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D015571:Follicular Fluid / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009994:Osmolar Concentration; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values
chemical_list: D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone