Cortisol Inactivation by 11β-Hydroxysteroid dehydrogenase-2 May Enhance Endometrial Angiogenesis via Reduced Thrombospondin-1 in Heavy Menstruation

Context: Heavy menstrual bleeding (HMB; menorrhagia) impairs quality of life for women and requires medication or surgery. Because glucocorticoids inhibit angiogenesis in other organs, we hypothesized that endometrium of women with HMB is subject to decreased local glucocorticoid exposure and enhanced angiogenesis, thereby increasing menstrual bleeding. Design: Endometrium was collected from 29 women with menstrual complaints. Menstrual blood loss was measured by alkaline-hematin assay (n = 12, > 80 ml (HMB); n = 17, < 80 ml). Quantitative RT-PCR for thrombospondin-1 (TSP-1) and glucocorticoid-metabolizing enzymes, 11β-hydroxysteroid dehydrogenases-1 and -2 (11βHSD1,2) was performed. Glucocorticoid effects on endometrial stromal cells and uterine endothelial cells (UECs) were determined. RNA interference studies in UECs examined the effect of TSP-1 ablation on cortisol action. Results: Secretory phase endometrium mRNA levels for the cortisol inactivating enzyme 11βHSD2 were higher [3.78 ± 1.29 vs. 1.40 ± ...