title: Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells.
abstract: Porcine granulosa cells (GC) produce insulin-like growth factor (IGF) binding protein (BP)-3 and IGFBP-2 in culture. A gonadotropin, follicle-stimulating hormone (FSH), dramatically inhibited GC production of these IGFBPs in control cultures and in cultures stimulated by insulin plus epidermal growth factor (EGF) or IGF-I plus EGF. Stimulators of adenylate cyclase (forskolin, cholera toxin) and a derivative of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate, inhibited IGFBP synthesis in a manner similar to FSH. In contrast, the antagonist of cAMP action, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], significantly stimulated production of IGFBP-3 and IGFBP-2 compared with controls. This stimulatory effect of (R)-p-cAMPS was counteracted by cotreatment with FSH in a dose-dependent manner. Finally, treatment of GC cultures with FSH plus 3-isobutyl-1-methylxanthine resulted in a significant reduction in cellular content of mRNA coding for IGFBP-3 with no change in IGFBP-2 mRNA. In summary, agents that elevate intracellular cAMP were found to mimic the effects of FSH on IGFBP production.
authors.affiliation: Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
authors.forename: R W
authors.initials: RW
authors.lastname: Grimes
authors.forename: S E
authors.initials: SE
authors.lastname: Samaras
authors.forename: J A
authors.initials: JA
authors.lastname: Barber
authors.forename: S
authors.initials: S
authors.lastname: Shimasaki
authors.forename: N
authors.initials: N
authors.lastname: Ling
authors.forename: J M
authors.initials: JM
authors.lastname: Hammond
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013002:Somatomedins / Q000096:biosynthesis / Q000235:genetics; D013552:Swine
chemical_list: D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP