Somatomedin-C as an amplifier of follicle-stimulating hormone action: enhanced accumulation of adenosine 3',5'-monophosphate

摘要: Somatomedin-C (Sm-C) has recently been found to amplify the FSH-mediated acquisition of granulosa cell progestin biosynthetic capacity, aromatase activity, and LH receptors, an effect distinct from its established replicative property. To further characterize cellular mechanism(s) underlying synergistic interaction Sm-C with FSH, we have set out evaluate intermediary role cAMP in this regard. Isolated cells immature hypophysectomized diethylstilbestrol-treated rats were cultured for up 3 days under serum-free conditions. The basal extracellular accumulation remained unchanged response treatment highly purified (50 ng/ml). However, concurrent increasing concentrations (0.3-50 ng/ml) Sm-C, produced dose- time-dependent increments FSH-stimulated cAMP, apparent median effective dose (ED50; mean +/- SE) 5.1 0.6 ng/ml, a maximal 8.8-fold greater than that induced by FSH alone, minimal time requirement 1-2 days. Given constant concentration resulted 1.7-, 5.8-, 4.3-fold increases 10, 30, 100 ng/ml respectively. ability augment was evident and, fact, enhanced ZK62711 (Rolipram; X 10(-6) M)-induced blockade cAMP-phosphodiesterase activity. Decreasing dilutions (1:64,000 1:1,000) monoclonal antibody raised against (sm 1.2) progressive complete immunoneutralization suggesting specificity action. Taken together, these findings suggest acting at nanomolar compatible receptor binding affinity (0.6-2.0 nM), is capable amplifying time- dose-dependent manner. These observations action exerted, least part, site(s) proximal generation.