| Summary: | Prostaglandin F2 (PGF2) secretion is lowest at mid-cycle and highest on day 15 at luteolysis in the cycling guinea pig uterus, and is inversely related to serum progesterone levels. An increase in 17- oestradiol (E2) occurs towards the end of the cycle. The guinea pig cDNAs for cyclooxygenase 2 (COX-2), 15-hydroxyprostaglandin dehydrogenase (PGDH) which catabolises PGF2, and a fragment of cyclooxygenase-1 (COX-1) were cloned. The effect of steroids on uterine PGF2 metabolism in endometrial primary cultures was investigated. COX-2 mRNA expression is correlated to PGF2 secretion. In epithelial cells steroid-modulated changes were observed; the addition of medroxyprogesterone acetate (MPA) to E2-primed cells led to a decrease, and the addition of E2 to MPA-primed cells to an increase, in COX-2 mRNA expression and PGF2 secretion. In contrast, steroid-modulated changes in PGDH transcripts were observed in stromal cells, and were upregulated by the addition of MPA to E2-primed cells. COX-1 transcripts were low and unaffected by treatment in both cell types. The in vitro observations were in keeping with the secretory profile seen in vivo in the cycling guinea pig uterus and suggest a differential role for the uterine stroma and epithelium, the former acting to remove (via PGDH), and the latter to produce (via COX-2) biologically active prostaglandin.;PGDH, COX-2 and COX-1 mRNA and protein expression were also analysed in uterine sections of the cycle and pregnancy. COX-1 mRNA expression was present during the cycle and pregnancy, and upregulated during late pregnancy. COX-1 protein was localised to the whole uterus except during early pregnancy. COX-2 mRNA was detected only at luteolysis. During pregnancy PGDH mRNA was expressed as a layer around the foetus, initially in the endometrial stroma (day 15) and later the luminal epithelium (day 50), providing a barrier between foetally derived PGs and the myometrium. The in vivo results confirmed the in vitro findings and indicate that COX-2 is responsible for the rise in uterine PG output seen during the cycle, and COX-1 during pregnancy.
|
|---|
