Involvement of CRH and hCG in the induction of aromatase by cortisol in human placental syncytiotrophoblasts

Abstract

Introduction: Increased estrogen production in placenta towards the end of gestation plays a pivotal role in the onset of human labor. Estrogen transforms myometrium from a quiescent to a contractile status. Glucocorticoids have been shown to induce estrogen production through the transcription factor specificity protein 1 (Sp1)-mediated induction of aromatase transcription upon elevation of cyclic adenosine mono-phosphate (cAMP) level in human placental syncytiotrophoblasts. However, it is unclear how glucocorticoids activate cAMP pathway thereby inducing aromatase expression in human placental syncytiotrophoblasts.

Material and methods: We investigated this issue in cultured primary human placental syncytiotrophoblasts prepared from placentas collected at term without labor.

Results: We demonstrated that cortisol (0.01-1 μM) dose-dependently increased corticotropin-releasing hormone (CRH) and human chorionic gonadotropin (hCG) α/β subunit expression and their production in the syncytiotrophoblasts. The induction of intracellular cAMP level, Sp1 expression, Sp1 enrichment at the aromatase promoter as well as aromatase expression by cortisol could be partially attenuated by either hCG antibody (1:100) or CRH receptor antagonist α-helical-CRH (1 μM), and further attenuated by combination of hCG antibody and α-helical-CRH.

Conclusions: Cortisol increases aromatase expression via induction of CRH and hCG production and subsequent elevation of cAMP level and enrichment of Sp1 at the aromatase promoter in human placental syncytiotrophoblasts. These findings may account for the parallel increases of cortisol and estrogen production prior to the onset of parturition.

Keywords: Aromatase; CRH; Cortisol; Estrogen; Placenta; hCG.