Dexamethasone‐induced Changes in Endometrial Growth and Inducible Nitric Oxide Synthase During Decidualization in Rats

Abstract

1. The present study investigated the time-dependent inhibitory responses of endometrial growth and inducible nitric oxide synthase (iNOS) to dexamethasone during deciduoma development that was surgically induced on day 4 of pseudopregnancy (PG). 2. Groups of rats (n = 6) were subcutaneously injected with dexamethasone (1.5 mg/rat per day) for 3 days (PG days 1-3, 4-6, 7-9, 10-12 and 12-15). Rats in each group were killed 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 protein band), which peaked after PG days 4-6 and 7-9 pretreatments. 4. Endometrial matrix metalloproteinases (72 and 92 kDa) activity profiles displayed maximal reductions (36 and 53%, respectively) following PG days 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 most pronounced during decidual development (PG days 4-9). Minor reductions in these endometrial parameters occurred before deciduoma induction (PG days 1-3) and during deciduoma regression (PG days 10-15). 6. These results indicate that, in the endometrium, the iNOS/endogenous nitric oxide system may be linked to the biochemical and metabolic mechanisms responsible for the developmental responsiveness of the deciduoma to dexamethasone exposure. These time-dependent changes in endometrial growth and iNOS apparently were not mediated by progesterone.

Influence of progesterone on endometrial nitric oxide synthase expression

“…This inhibitory effect of RU486 on eNOS may be due to the mixed agonist and antagonist properties of RU486 (32). At high concentrations RU486 can have agonistic effects on the glucocorticoid receptors (33), and as previously demonstrated by others glucocorticoids can inhibt the expression of eNOS (34) and iNOS (35) in endothelial cells and iNOS in the rat uterus (36). The lack of effect of RU 486 on iNOS expression is similar to our previously reported finding in HES cells, where ICI 182,780, an estrogen receptor antagonist in high concentrations stimulated the expression of iNOS protein while inhibiting eNOS expression (6).…”

Expression and Regulation of Inducible Nitric Oxide Synthase from Human Primary Airway Epithelial Cells

“…In asthma, exhaled NO levels are reduced by corticosteroid therapy (17), suggesting that human iNOS is regulated by steroids. Murine iNOS expression is readily inhibited by steroids (13,18), and many studies have demonstrated the inhibitory effects of steroids on rat models of iNOS induction (19)(20)(21). However, the effect of steroids on the regulation of the human isoform of iNOS is more ambiguous.…”