Endocrine Abstracts

Introduction: Glucocorticoids may exert important actions in early pregnancy on the invading trophoblast. The local actions of glucocorticoids can be modulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes which catalyse inter-conversion of cortisol with its inert metabolite, cortisone. Although two cloned 11β-HSD isoenzymes are known to be expressed in the term placenta, their expression and activity have not been well characterised in the first trimester placenta.

Methods: The effects of acute (6 h) and chronic (16 h) exposure to cortisol and cortisone on the motility of the SGHPL4 extravillous trophoblast cell line were investigated in the presence and absence of epidermal growth factor (EGF) using time lapse microscopy. Invasion was assessed by culturing SGHPL4 cells on gelatine-coated micro-carrier beads embedded in fibrin gels for 48 h prior to image analysis (Image Pro Plus software). Expression of 11β-HSD enzymes was assessed in first trimester placental tissue by western blot analysis and in chorionic villi using immunohistochemistry.

Results and discussion: While acute treatment with both cortisol and cortisone increased SGHPL4 motility, there was no response to chronic steroid treatment. EGF significantly stimulated cell motility, but this response was not affected by co-treatment with either cortisol or cortisone. Although EGF stimulated both the number and length of invasive processes invading into fibrin gels, treatment with cortisol or cortisone had no effect on either basal or EGF-stimulated cell invasion. Western blot analysis confirmed expression of 11β-HSD2 in first trimester placental tissue and immunohistochemistry localised expression of the 11β-HSD2 protein to the syncytiotrophoblast. Enzyme assays confirmed NAD⁺-dependent inactivation of cortisol by 11β-HSD2 in first trimester placental tissue, where it might modulate the effects of cortisol on extravillous trophoblast motility. A comparison will be made of cortisol metabolism between tissue obtained from pregnancies at the highest and lowest risk of developing pre-eclampsia, as determined by uterine artery Doppler resistance indices.