title: Immunosuppressive levels of glucocorticoid block extrauterine luteolysins in the rat.
abstract: Leukocytes, normal constituents of the corpus luteum, release prostaglandins (PGs), superoxide, and hydrogen peroxide (H2O2) upon activation. These products appear to mediate luteolysis, and it has been postulated that activated leukocytes serve a role in corpus luteum regression. Glucocorticoids prevent leukocyte infiltration and activation by inhibiting cytokine production, secretion, and action, and also inhibit eicosanoid synthesis. The objective of the present studies was therefore to assess whether glucocorticoid would influence luteal regression in the rat. Ovulation and pseudopregnancy were synchronized in prepubertal 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 regression in uterine-intact animals when administered daily from early in pseudopregnancy for as long as treatment was continued (up to Day 17). Immunosuppressive effects of dexamethasone were evident in the inhibition of estrogen-induced infiltration of eosinophils, as shown by abrogation of estrogen-induced uterine peroxidase activity, and high continuous levels of dexamethasone were necessary to block luteolysis. Hysterectomy 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 Day 19. Dexamethasone treatment of hysterectomized rats from Day 12 until Day 15 or 18 blocked the decline in serum progesterone levels. Dexamethasone treatment did not block the decrease in serum progesterone levels induced within 24 h by PGF2 alpha in uterine-intact animals on Day 9 or in hysterectomized animals on Day 19.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Ob/Gyn, Yale University School of Medicine, New Haven Connecticut 06510.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: J C
authors.initials: JC
authors.lastname: Riley
authors.forename: H R
authors.initials: HR
authors.lastname: Behrman
mesh_terms: D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D007044:Hysterectomy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D003341:Luteolysis / Q000187:drug effects* / Q000502:physiology; D010544:Peroxidases / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D051381:Rats; D014599:Uterus / Q000502:physiology*
chemical_list: D007166:Immunosuppressive Agents; D011374:Progesterone; D003907:Dexamethasone; D015237:Dinoprost; D010544:Peroxidases; D015232:Dinoprostone