HUMAN ENDOMETRIAL STROMAL CELLS GENERATE UNCOMBINED ALPHA-SUBUNIT FROM HUMAN CHORIONIC-GONADOTROPIN, WHICH CAN SYNERGIZE WITH PROGESTERONE TO INDUCE DECIDUALIZATION

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 s tudy, we demonstrate that glycoprotein hormone free a-subunit potentia tes 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 alp ha-subunit. However, in the present study we show that decidualizing e ndometrial cells actively generate uncombined alpha-subunit by dissoci ating hCG. The amount of dissociated alpha-subunit could fully account for the stimulatory activity observed with hCG. Active dissociation o f hCG was dependent on the presence of endometrial cells and did not o ccur in conditioned medium, excluding involvement of a stable secreted factor such as a protease. In addition to dissociated alpha- and beta -subunits, minor amounts of beta-core and alpha-fragments were detecte d as degradation products during active dissociation. We also observed an increase in beta-immunoreactivity that coeluted with hCG on size-e xclusion gel chromatography, indicating that a portion of the still di meric hCG may have been nicked in the dissociation process. However, u sing an assay with specificity for nicked hCG, we showed that dissocia tion of hCG was not produced from a pool of preexisting nicked hCG. Th ese findings more firmly establish the concept that gonadotropin hormo ne free alpha-subunit plays a role in the regulation of human endometr ial cell differentiation. In addition, identification of the various p roducts formed by incubation of hCG with decidualizing cells yielded i nsight into the mechanism of hCG degradation, and may explain some act ivity previously ascribed to hCG.