PROMEGESTONE (R5020) AND MIFEPRISTONE (RU486) BOTH FUNCTION AS PROGESTATIONAL AGONISTS OF HUMAN GLYCODELIN GENE-EXPRESSION IN ISOLATED HUMAN EPITHELIAL-CELLS
Rn. Taylor et al., PROMEGESTONE (R5020) AND MIFEPRISTONE (RU486) BOTH FUNCTION AS PROGESTATIONAL AGONISTS OF HUMAN GLYCODELIN GENE-EXPRESSION IN ISOLATED HUMAN EPITHELIAL-CELLS, The Journal of clinical endocrinology and metabolism, 83(11), 1998, pp. 4006-4012
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.