DEXAMETHASONE-INDUCED CHANGES IN ENDOMETRIAL GROWTH AND INDUCIBLE NITRIC-OXIDE SYNTHASE - DURING DECIDUALIZATION IN RATS

1. The present study investigated the time-dependent inhibitory respon ses of endometrial growth and inducible nitric oxide synthase (iNOS) t o dexamethasone during deciduoma development that was surgically induc ed on day 4 of pseudopregnancy (PG). 2. Groups of rats (n = 6) were su bcutaneously injected with dexamethasone (1.5 mg/rat per day) for 3 da ys (PG days 1-3, 4-6, 7-9, 10-12 and 12-15), Rats in each group were k illed on the last injection day, 3. Dexamethasone produced comparable temporal inhibitory changes in endometrial growth (wet weight, protein and DNA concentrations; P<0.0001) and in iNOS activity (130 kDa prote in band), which peaked after PG days 4-6 and 7-9 pretreatments. 4. End ometrial matrix metalloproteinases (72 and 92 kDa) activity profiles d isplayed maximal reductions (36 and 53%, respectively) following PG da ys 4-6 pretreatment, Serum progesterone levels were equally (P<0.0001) but asynchronously inhibited by dexamethasone on PG days 9 and 12, 5. Dexamethasone inhibition of endometrial growth and in situ iNOS was m ost pronounced during decidual development (PG days 4-9), Minor reduct ions in these endometrial parameters occurred before deciduoma inducti on (PG days 1-3) and during deciduoma regression (PG days 10-15), 6. T hese results indicate that, in the endometrium, the iNOS/endogenous ni tric oxide system may be linked to the biochemical and metabolic mecha nisms responsible for the developmental responsiveness of the deciduom a to dexamethasone exposure, These time-dependent changes in endometri al growth and iNOS apparently were not mediated by progesterone.