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Endogenous H2S is produced from L-cysteine principally through the activity of two enzymes,cystathionine--lyase (CSE) and cystathionine--synthetase (CBS).CBS and CSE have been identified in human placenta.However, the physiological functions of H2S in the placenta remain unclear.Corticotropin-releasing hormone (CRH) plays pivotal roles in maintain pregnancy and initiation of labor in human.In the present study, we investigated whether H2S modulate the synthesis and release of CRH in cultured placental trophoblasts.Treatment of cultured placental cells with sodium hydrosulfide, a H2S donor, resulted in a dose-dependent decrease in CRH mRNA expression and CRH content in culture media and cell lysis.L-cysteine treatment also caused a decrease in CRH content in cell lysis and culture media as well as mRNA expression in placenta.The effects of L-cysteine were blocked by either CSE inhibitor PAG or CBS inhibitor AOAA.D-cysteine had no effect on CRH mRNA expression and production in placental cells.The results suggested that endogenous H2S produced locally regulate CRH synthesis and secretion in placenta, and, consequently, involvement in maintenance of pregnancy and control of parturition in humans.