Abnormal expression of 11beta-HSD type 2 in human pituitary adenomas: a prereceptor determinant of pituitary cell proliferation

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by inhibition of cell proliferation. Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert cortisol (F) and inactive cortisone (E), and are thus able to modulate GC action at an autocrine level. Previously, we have demonstrated absent expression of 11beta-HSD2 in normal pituitaries; however, in a small number of pituitary tumors analysed, 11beta-HSD2 was readily demonstrable. Here we have used real-time RT-PCR to quantify expression of mRNA for 11beta-HSD1 and 2 in 105 human pituitary tumors and have performed enzyme expression and activity studies in primary pituitary cultures. Overall, pituitary tumors expressed lower levels of 11beta-HSD1 mRNA compared with normals (0.2-fold, P