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 endometrium is glycodelin, a glycoprotein previously referred to as PP14. Although the precise function of this protein is unknown, its unique glycosylation pattern is believed to affect immunomodulatory activity during human embryonic implantation and inhibition of sperm-egg binding after ovulation. Having confirmed the expression of glycodelin in secretory endometrial glands, we used purified endometrial epithelial cell cultures to demonstrate the hormonal regulation of glycodelin synthesis and secretion. The findings were corroborated by transiently transfecting 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 endometrial cells, progestins and antiprogestins both act as agonists on the in vitro expression of this endometrial gene. Our findings provide insight 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 glycodelin gene promoter.
Taylor
R N
RN
Unité de Recherches Hormones et Reproduction, INSERM U135, Université Paris-Sud, Hôpital de Bicêtre APHP, Le Kremlin-Bicêtre, France.
Savouret
J F
JF
Vaisse
C
C
Vigne
J L
JL
Ryan
I
I
Hornung
D
D
Seppälä
M
M
Milgrom
E
E
D004353:Drug Evaluation, Preclinical; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D000071816:Glycodelin; D006023:Glycoproteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000235:genetics*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D014162:Transfection
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; D015735:Mifepristone; D011397:Promegestone