Molecular Human Reproduction, Vol. 5, No. 6, 573-580,
June 1999
© 1999 European Society of Human Reproduction and Embryology
Cyclic AMP- and differentiation-dependent regulation of the proximal 
HCG gene promoter in term villous trophoblasts
1 Department of Obstetrics and Gynecology, and 2 Department of Internal Medicine IV, University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria
Although the regulatory mechanisms controlling 
and ß human chorionic gonadotrophin (HCG) expression have been investigated in choriocarcinoma cell model systems, little is known about the regulation of HCG subunit synthesis in non-tumourigenic trophoblasts. We therefore investigated HCG mRNA transcription in villous cytotrophoblasts isolated from term placentae and have shown for the first time that the proximal HCG gene promoter is functional in these cells. By establishing conditions which allow efficient transient transfection of immunopurified cells, we have demonstrated that a 363 bp sequence in the proximal 5' flanking region of the HCG gene is sufficient to direct trophoblast-specific expression of a luciferase reporter. After 12–60 h cultivation, an increase in endogenous HCG mRNA expression could be detected, indicating that aggregated villous trophoblasts undergo biochemical differentiation. Concomitantly, we observed induction of HCG promoter-driven luciferase activity, suggesting that the 363 bp sequence of the proximal 5' flanking region is sufficient to direct differentiation-dependent increase of HCG mRNA. Continuous luciferase expression required functional cAMP-response elements (CREs), since deletion of both recognition sequences eliminated differentiation-dependent transcription of the reporter. Elevation of cAMP values increased transcription of the wild-type construct; however, it did not affect promoter activity of the mutant plasmid. Moreover, we have demonstrated that during in-vitro differentiation, CREs interacted with increasing amounts of phosphorylated activating transcription factor/cyclic AMP response element-binding protein (ATF-1/CREB-1) suggesting that these cAMP-dependent DNA-binding factors are major determinants in regulating HCG gene expression in villous trophoblasts.
HCG gene promoter/ATF-1/cAMP response/transfection/villous trophoblast
3 To whom correspondence should be addressed
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