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Human Endometrial Stromal Cells Generate Uncombined -Subunit from Human Chorionic Gonadotropin, Which Can Synergize with Progesterone to Induce Decidualization

Unit of Glycobiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Diana L. Blithe, Ph.D., Contraception and Reproductive Health Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 61E, Room 8B13, Bethesda, Maryland 20892. E-mail: BlitheD{at}hd01.nichd.nih.gov

During the secretory phase of the menstrual cycle, endometrial stromal cells differentiate into decidual cells, which play a crucial role in implantation and maintenance of pregnancy. In this and our previous study, we demonstrate that glycoprotein hormone free -subunit potentiates progesterone-mediated decidualization of human endometrial stromal cells in vitro. Although addition of intact hCG to cultures resulted in stimulatory activity, its potency was 20-fold less than that of -subunit. However, in the present study we show that decidualizing endometrial cells actively generate uncombined -subunit by dissociating hCG. The amount of dissociated -subunit could fully account for the stimulatory activity observed with hCG. Active dissociation of hCG was dependent on the presence of endometrial cells and did not occur in conditioned medium, excluding involvement of a stable secreted factor such as a protease. In addition to dissociated - and ß-subunits, minor amounts of ß-core and -fragments were detected as degradation products during active dissociation. We also observed an increase in ß-immunoreactivity that coeluted with hCG on size-exclusion gel chromatography, indicating that a portion of the still dimeric hCG may have been nicked in the dissociation process. However, using an assay with specificity for nicked hCG, we showed that dissociation of hCG was not produced from a pool of preexisting nicked hCG. These findings more firmly establish the concept that gonadotropin hormone free -subunit plays a role in the regulation of human endometrial cell differentiation. In addition, identification of the various products formed by incubation of hCG with decidualizing cells yielded insight into the mechanism of hCG degradation, and may explain some activity previously ascribed to hCG.

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