Follicle-stimulating hormone (FSH) stimulates the proliferation, survival, and estradiol synthesis of granulosa cells by binding to their G protein-coupled receptors. Although FSH activates sphingosine kinase-1 (SPHK1) to induce sphingosine-1-phosphate (S1P) synthesis, which is required to mediate the proliferative and survival effect of this gonadotrophin, the mechanisms, and the role of S1P in estradiol synthesis have not been reported. This study aimed to evaluate the importance of FSH-induced S1P synthesis as a mediator of the effects of this gonadotrophin on granulosa cell viability and steroidogenesis and to determine if FSH-induced S1P synthesis depends on estradiol, cAMP, PKA, or PKC.
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