Submission Number: BRE-4-35-24
Abstract Number: 393
SUPPRESSION OF THE DECIDUAL REACTION BY INHIBITION OF ENDOMETRIAL 11-HYDROXYSTEROID DEHYDROGENASE.
Brendan J Waddell and Peter J Burton
Department of Anatomy & Human Biology, The University of Western Australia, Nedlands, Perth, W.A. 6907 Australia 1
Endometrial decidualization in rodents is a crucial part of the implantation process and is characterised by marked changes in the morphology and function of endometrial stromal cells. Decidualization is promoted by a range of endocrine signals, including progesterone and prostaglandins, but is impeded by glucocorticoids (GCs). The biological actions of GCs are exerted via the GC receptor, access to which can be controlled by the local expression of the 11-hydroxysteroid dehydrogenase enzymes (11-HSD types 1 and 2) which interconvert active and inactive GCs. We have previously reported that 11-HSD-2 is expressed in endometrial stromal cells in an estrogen-dependent manner (Endocrinology 139:376-382). In the present study we tested the hypothesis that endometrial 11-HSD-2 locally inhibits GC levels to facilitate decidualization. On the morning of day 5 of pseudopregnancy (PSP) a cannula was inserted into the ovarian end of one uterine horn and either dexamethasone (DEX; LD: 10 ng/ml; HD: 100 ng/ml), the 11-HSD inhibitor carbenoxolone (CBX; 5 g/ml) or vehicle (propylene glycol:saline:ethanol; 50:40:10) were infused via a miniosmotic pump (1 l/hr) for 4 days. CBX was also infused into a uterine horn of PSP rats adrenalectomized 3 days earlier (CBX/ADX). Infused and non-infused uterine horns were collected on day 9 of PSP; wet weight and histological analysis were used to assess the extent of decidualization. Administration of vehicle alone induced a decidual reaction and resulted in an 8-fold increase in wet weight of the infused uterine horn (1082 49 mg) compared to the non-infused horn (138 8 mg). In contrast, infusion of DEX (HD) or CBX induced only a 2- to 3-fold increase in weight, and histological analysis showed that this reduced weight gain was associated with a marked reduction in decidualization. The full effect of CBX required the presence of intact adrenals, showing that increased exposure to endogenous GCs via inhibition of endometrial 11-HSD suppressed decidua formation. These data support the hypothesis that a low GC environment (via endometrial 11-HSD-2 expression) is necessary for full decidualization. We suggest that endometrial 11-HSD-2 facilitates decidualization by preventing suppression of local prostaglandin synthesis by endogenous GCs. .
Keywords: uterus, decidualization, glucocorticoids, 11-HSD
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