TEMPORAL GLUCOCORTICOID TREATMENT - MODULATION OF PERIODIC ENDOMETRIAL RESPONSES DURING DECIDUALIZATION AND PREGNANCY IN RATS

The synthetic glucocorticoid, dexamethasone (Dex) was administered sub cutaneously (1.5 mg/day/rat) in 3-days pretreatment regimens (Days 2-4 , 4-6, 6-8, 8-10 and 10-12) to pseudopregnant rats in which decidualiz ation was surgically induced and to pregnant rats. Variability in endo metrial growth during decidualization and in the fetoplacental homeost asis of pregnancy was assessed at the end of each treatment period (Da ys 4, 6, 8, 10 and 12). During decidualization, endometrial growth (we t weight, protein and DNA) displayed significant (p < 0.05) time-depen dent inhibitory profiles which rose steeply from Day 4 to Day 6 and de clined thereafter to Day 10 in fairly well defined linear patterns. Fo r the endometrial enzymes (isocitrate dehydrogenase, alkaline phosphat ase and the matrix metalloproteinases-72 and 92 kDa), although the inh ibitory patterns were inconsistent, a Days 6-8 treatment regimen seeme d to be critical. By contrast Dex treatment induced progressive inhibi tion in serum progesterone concentrations from Day 2, to peak levels a t Day 12. This indicates that time-related Dex inhibition of endometri al growth appeared not to be progesterone-mediated since the endometri al and progesterone inhibitory profiles were not in synchrony. The inh ibitory effect of Dex under the pregnancy status demonstrated that bir th potentials, fetal and placental weights, all had similar response p atterns which rose from Day 4 to Day 8 and then underwent reductions t o Day 12. Collectively, the results indicate that there was time depen dency in growth inhibition by Dex at the endometrial and fetoplacental levels. Maximal sensitivity to drug exposure essentially coincided wi th the immediate post-traumal (decidualization) and postimplantation ( pregnancy) periods. (C) 1997 Elsevier Science Inc.