Molecular events in the endometrium. Rapid down-regulation of CD63 transcription by progesterone in human endometrial stromal cells

Differentiation of endometrial stromal cells (decidualization) plays a crucial role in embryo implantation and maintenance of pregnancy. While progesterone is a key factor in regulating endometrial cell decidualization, the molecular mechanisms remain unclear. In the present study, we investigated the effect of gene transcription in human endometrial stromal cells (ESC) by progesterone, oestrogen or vehicle using the polymerase chain reaction-based differential display methodology. A transcript which is down-regulated by progesterone, but not by vehicle and oestrogen, was identified from a differential display band and the progesterone sensitivity of its expression was verified in Northern blot analysis. The level of the gene expression in progesterone-treated ESC was ~60% of that in the vehicle- and oestrogen-treated ESC. This cDNA was revealed to be human CD63 antigen, a recently identified member of the transmembrane 4 superfamily. The inhibitory effect of progesterone is observed within 30 min after hormone treatment. In human endometrium, CD63 mRNA levels were significantly decreased (P < 0.05) during the secretory phase compared with levels during the proliferative phase. This down-regulation of CD63 in vivo elevated levels of progesterone in the secretory phase. These results suggest that CD63 transcription is down-regulated by progesterone in human endometrium.