AJP - Endocrinology and Metabolism, Vol 262, Issue 4 E497-E503, Copyright © 1992 by American Physiological Society
Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells
R. W. Grimes, S. E. Samaras, J. A. Barber, S. Shimasaki, N. Ling and J. M. Hammond
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
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.
