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BOR - Papers in Press, published online ahead of print December 20, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.056960
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Submitted September 1, 2006
Returned for revision October 9, 2006
Accepted December 18, 2006

Pregnancy


Upregulation of Placental Indoleamine 2,3-Dioxygenase by Human Chorionic Gonadotropin

Z. M. Lei , M. Yang , X. Li , O. Takikawa , and C. V. Rao *

* To whom correspondence should be addressed. E-mail: cvrao001{at}louisville.edu.

Abstract
We tested the hypothesis that hCG can upregulate human trophoblast indoleamine 2, 3- dioxygenase (INDO), which catalyzes the breakdown of tryptophan in villous circulation. The results revealed that it can. Treatment of human t rophoblasts with hCG resulted in a time and dose dependent increase in INDO mRNA and protein levels and its enzyme activity. The hCG effect was hormone specific and require the dimer conformation of hCG. The hCG effect required its receptors and was mediated by a cAMP dependent, but protein kinase A independent, mitogen-activated protein kinase 3/1 (MAPK3/1) signaling mechanism. In summary, the present data demonstrate a novel hCG effect on human placental INDO, which probably plays a key role at maternal fetal interface in preventing fetal rejection.

Key words: Mechanisms of Hormone Action • Pregnancy • Human chorionic gonadotropin • Placenta • Trophoblast


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