Divergent actions of prostaglandins-E2 and -F2 alpha on the regulation of insulin-like growth factor-binding protein-3 in luteinized granulosa cells.

Abstract

Insulin-like growth factor (IGF)-I synergizes with gonadotropin to further stimulate ovarian steroidogenesis. In contrast, the IGF-binding proteins (IGFBPs) produced by granulosa cells have been shown to antagonize the stimulatory actions of the IGFs and gonadotropins. The purpose of the present study was to examine the effects on IGFBP-3 production of prostaglandin (PG)-E2, a compound known to stimulate luteal function and prevent/delay luteal regression (a luteotropic compound), and PGF2 alpha, a compound known to be luteolytic. PGF2 alpha significantly stimulated IGFBP-3 production to 2.6-fold of control (P < 0.05) while PGE2 attenuated its production to half of control (P < 0.05). In contrast to the effects of IGFBP-3, PGE2 stimulated progesterone production to 8-fold of control (P < 0.05) while PGF2 alpha had no effect. Possible mechanisms of action of PGE2 and PGF2 alpha were also examined. PGE2, but not PGF2 alpha, stimulated cAMP accumulation which has been previously shown to inhibit IGFBP-3 production. PGF2 alpha is suspected to act via activation of protein kinase-C. However, a phorbol ester did not mimic PGF2 alpha's action toward IGFBP-3. This study demonstrated that PGE2 and PGF2 alpha conversely modulate IGFBP-3 production. Since IGFBPs have been shown to antagonize gonadotropin and IGF actions, this action of the prostaglandins may impact on the synergism between IGFs and gonadotropin necessary for follicular growth and luteal function.