Mechanical vagino-cervical stimulation (vcs) or mating stimulates hypothalamic neurons that regulate pulsatile secretion of gonadotropin-releasing hormone and the gonadotropins which affect decidualization, an essential for successful mammalian pregnancy, via induced ovarian steroidogenesis. Progesterone-regulated deciduomal growth is promoted by paracrine factors plus the uterine matrix metalloproteinases (MMPs) that remodel the decidual tissue, and nitric oxide (NO), a regulator of uterine vascularity. Dexamethasone (Dexa), a synthetic glucocorticoid, is an established inhibitor of uterine growth. The purpose of the study was to evaluate the time-related inhibitory effects of Dexa on (1) the enzymatic activities of MMPs, and of inducible nitric oxide synthase (iNOS), an isoform involved in NO biosynthesis; and (2) on progesterone secretion during decidual proliferation that was triggered by the neurogenic signals of copulomimetic vcs followed by deciduogenic stimulation via surgical uterine trauma during artificially-induced pseudopregnancy (PG). Female rats (210240 g; under 12L: 12D) were subjected to vcs (proestrus and estrus) and uterine trauma (day 4 PG) for PG/decidualization induction. Rats (n=6/group) were subcutaneously injected with Dexa (1.5 mg/day) for 3 days (PG day 13, 46, 79, 1012 and 1315). Animals were killed on the last injection day for analysis of serum progesterone by RIA, MMP activity by substrate zymography, and iNOS activity by western blot. Comparable temporal inhibition by Dexa was noted for decidual weights and iNOS activity which peaked after PG days 46 and 79. Decidual MMP (72 and 92 kDa) activities were maximally reduced following PG days 46 Dexa treatment. However, serum progesterone levels were equally (P<0.0001), but asynchronously inhibited by Dexa on PG days 9 and 12. The data indicate that deciduomal iNOS/NO system and MMP activity appeared to be linked to the overall decidual metabolic mechanism that responds to Dexa inhibition. The time-related reductions in decidual growth, iNOS and MMP activities were apparently not mediated by serum progesterone.
25 - 29 Apr 2009
European Society of Endocrinology