alexa Altered cyclic AMP-dependent human chorionic gonadotropin production in cultured human placental trophoblasts exposed to ethanol.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Steroids & Hormonal Science

Author(s): Karl PI, Divald A, Diehl AM, Fisher SE

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Abstract Chronic ethanol abuse during pregnancy can cause fetal injury, including the fetal alcohol syndrome (FAS). A contributing factor in this fetal injury may be the effect of ethanol on placental function. Previous studies have shown that ethanol treatment increases human chorionic gonadotropin (hCG) production by cultured human placental trophoblasts. In this study, we demonstrated that the stimulation of hCG production correlates with the ethanol concentration. Ethanol treatment enhanced intracellular adenosine 3':5'-cyclic monophosphate (cAMP) levels in response to either cholera toxin (CTX) or forskolin (FSK). Moreover, basal (i.e. unstimulated) cAMP levels were increased at 2 hr of ethanol exposure. However, this effect did not persist throughout the 24-hr incubation period. Therefore, ethanol treatment appears to induce increased hCG production, secondary to enhanced basal or stimulated cAMP production. The effect of ethanol was not associated with changes in Gs or Gi2 expression, as determined by northern blot and western blot analyses. In plasma membrane preparations from ethanol-treated cells, cAMP production was higher in response to Mn2+, a direct stimulator of adenylyl cyclase. Inclusion of Rp-cAMP, a protein kinase A inhibitor, eliminated the ethanol effect on hCG production. Treatment of cells with 8-Br-cAMP stimulated hCG production, but there was no difference between the ethanol-naive control and the ethanol-treated cells. These data suggest that ethanol treatment increases in vitro hCG production in human placental trophoblasts by enhancing cAMP production. Ethanol treatment appears to increase trophoblast adenylyl cyclase activity.
This article was published in Biochem Pharmacol and referenced in Journal of Steroids & Hormonal Science

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