Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells.
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.
Grimes
R W
RW
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Samaras
S E
SE
Barber
J A
JA
Shimasaki
S
S
Ling
N
N
Hammond
J M
JM
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
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP