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Endocrinology Vol. 144, No. 3 1108-1120
Copyright © 2003 by The Endocrine Society

ARTICLE

The Central Role of Human Chorionic Gonadotropin in the Formation of Human Placental Syncytium

M. Yang1, Z. M. Lei and Ch. V. Rao

Division of Research, Department of Obstetrics, Gynecology, and Women’s Health, University of Louisville Health Sciences Center, Louisville, Kentucky 40292

Address all correspondence and requests for reprints to: Dr. Ch. V. Rao, Department of Obstetrics, Gynecology, and Women’s Health, University of Louisville Health Sciences Center, Louisville, Kentucky 40292. E-mail: cvrao001{at}gwise.louisville.edu.

A number of trophoblast products, including human chorionic gonadotropin (hCG), can increase the formation of human placental syncytium through the differentiation of mononuclear cytotrophoblasts. The present study investigated the central role of hCG in this process by using antisense receptor phosphorothioate oligodeoxynucleotides (ODNs). Culturing cytotrophoblasts with the hCG/LH receptor antisense, but not sense, ODN resulted in a significant decrease in receptor protein levels and inhibited spontaneous as well as exogenous hCG induced increase in differentiation. The hCG/LH receptor antisense ODN also inhibited epidermal growth factor (EGF), TGF-{alpha}, leukemia inhibitory factor (LIF), but not 8-bromo-cAMP, induced increases in differentiation, suggesting that hCG is required for EGF, TGF-{alpha} and LIF, but not for the cAMP actions. Although antisense EGF receptor and LIF receptor ODNs inhibited EGF and LIF induced increase in differentiation, respectively, they were ineffective against hCG, suggesting that they use separate pathways, but they both converge on a common pathway requiring the hCG actions. Mechanism of action studies revealed that EGF treatment activates its receptors and MAPK, both of which are required for EGF to increase the differentiation, cAMP levels and activate protein kinase A. In summary, our results demonstrate that hCG is an autocrine and paracrine regulator that is required for EGF, TGF-{alpha}, and LIF, but not for cAMP to increase human placental syncytium formation. Direct activation of protein kinase A seems to bypass the hCG pathway, perhaps by targeting genes associated with the differentiation.




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