PROMEGESTONE (R5020) AND MIFEPRISTONE (RU486) BOTH FUNCTION AS PROGESTATIONAL AGONISTS OF HUMAN GLYCODELIN GENE-EXPRESSION IN ISOLATED HUMAN EPITHELIAL-CELLS

One of the most abundant protein products of human secretory endometri um is glycodelin, a glycoprotein previously referred to as PP14. Altho ugh the precise function of this protein is unknown, its unique glycos ylation pattern is believed to affect immunomodulatory activity during human embryonic implantation and inhibition of sperm-egg binding afte r ovulation. Having confirmed the expression of glycodelin in secretor y endometrial glands, we used purified endometrial epithelial cell cul tures to demonstrate the hormonal regulation of glycodelin synthesis a nd secretion. The findings were corroborated by transiently transfecti ng glycodelin gene promoter-reporter constructs into human epithelioid HeLa and Ishikawa cells. Our results indicate that glycodelin protein production by endometrial epithelial cells is directly up-regulated 4 - to 9-fold by progestins and antiprogestins in vitro. Transcriptional regulation of the glycodelin gene promoter expressed in HeLa cells is progesterone receptor-dependent. As observed in the primary endometri al cells, progestins and antiprogestins both act as agonists on the in vitro expression of this endometrial gene. Our findings provide insig ht into the regulation of this abundant endometrial protein and raise interesting questions about the physical nature of the interaction of agonist- and antagonist-bound progesterone receptors with the glycodel in gene promoter.