IMMUNOSUPPRESSIVE LEVELS OF GLUCOCORTICOID BLOCK EXTRAUTERINE LUTEOLYSINS IN THE RAT

Leukocytes, normal constituents of the corpus luteum, release prostagl andins (PGs), superoxide, and hydrogen peroxide (H2O2) upon activation . These products appear to mediate luteolysis, and it has been postula ted that activated leukocytes serve a role in corpus luteum regression . Glucocorticoids prevent leukocyte infiltration and activation by inh ibiting cytokine production, secretion, and action, and also inhibit e icosanoid synthesis. The objective of the present studies was therefor e to assess whether glucocorticoid would influence luteal regression i n the rat. Ovulation and pseudopregnancy were synchronized in prepuber tal rats by gonadotropin treatment. In uterine-intact rats, functional luteal regression, assessed from serum progesterone levels, began on Day 10 and was complete by Day 14. Dexamethasone blocked luteal regres sion in uterine-intact animals when administered daily from early in p seudopregnancy for as long as treatment was continued (up to Day 17). Immunosuppressive effects of dexamethasone were evident in the inhibit ion of estrogen-induced infiltration of eosinophils, as shown by abrog ation of estrogen-induced uterine peroxidase activity, and high contin uous levels of dexamethasone were necessary to block luteolysis. Hyste rectomy extended luteal function by several days, with maintenance of maximal serum progesterone levels up to Day 12; but serum progesterone levels were reduced about 50% by Day 16 and completely depressed by D ay 19. Dexamethasone treatment of hysterectomized rats from Day 12 unt il Day 15 or 18 blocked the decline in serum progesterone levels. Dexa methasone treatment did not block the decrease in serum progesterone l evels induced within 24 h by PGF2alpha in uterine-intact animals on Da y 9 or in hysterectomized animals on Day 19. Production of PGE, and PG F2alpha by ovarian luteal cellular dispersate was severely depressed b y dexamethasone. The prevention of luteolysis in hysterectomized rats by dexamethasone shows that extrauterine agents play a role in luteoly sis and are probably generated within the corpus luteum. The well-know n immunosuppressive properties of glucocorticoids and their ability to block PG synthesis implicates intraluteal parenchymal or leukocyte-cy tokine interactions as potential mediators of luteolysis.