Fig. 4.

P₄/PR regulates 20α-HSD in the uterus via modulation of the miR-200-STAT5b axis. (A–D) Ovariectomized mice were injected with P₄ (1 mg) or with vehicle; uterine tissues were harvested 24 h later. P₄ treatment inhibited miR-200a expression (A) induced STAT5b mRNA (B) and protein (C) and inhibited 20α-HSD mRNA (D). (E–H) Timed pregnant 15.5 dpc mice were injected subcutaneously with the PR antagonist RU486 (200 μg) or with vehicle. RU486 injected mice were killed upon the preterm birth of one pup; a vehicle-injected control was killed immediately afterward and myometrial tissues were isolated. RU486 treatment increased miR-200a (E), inhibited STAT5b mRNA (F) and protein (G), and induced 20α HSD mRNA (H) expression. Expression of each miRNA/mRNA was determined by qRT-PCR, normalized to U6/GAPDH, and expressed as fold-change over vehicle-treated controls. Mean ± SEM values are shown. Student t test, *P < 0.05, n = 5 mice per treatment group. (I) Schematic diagram of the regulation of PR function during pregnancy and labor via the miR-200/STAT5b/20α-HSD axis.