Modulation of the action of chorionic gonadotropin in the baboon (Papio anubis) uterus by a progesterone receptor antagonist (ZK 137.316)

Signals from the developing mammalian blastocyst rescue the corpus luteum ( CL) and modulate the uterine environment in preparation for implantation an d early pregnancy. Our previous studies demonstrated that both short- and l ong-term administration of chorionic gonadotropin (CG) markedly alters the morphology and the biochemical activity of the receptive endometrium, Becau se the effects of CG were superimposed on a progesterone-primed endometrium , this study was undertaken to determine if the inhibition of progesterone action by progesterone receptor antagonists (PR alpha) in intact and ovarie ctomized baboons would alter the action of CG on the endometrium at the tim e of uterine receptivity. In the short-term hCG-treated baboons, the PR alp ha reduced the epithelial plaque reaction, completely inhibited alpha-smoot h muscle actin (alpha SMA) expression in stromal fibroblasts, and induced t he reappearance of the progesterone (PR) and estrogen (ER alpha) receptors in epithelial cells, However, this treatment protocol had no effect on the expression of glycodelin in the glandular epithelium. In contrast, glycodel in expression in addition to alpha SMA was suppressed in the ovariectomized animals. In the long-term hCG-treated baboons, the PRa had a similar effec t on both alpha SMA, PR, and ER, In addition, this treatment also resulted in an inhibition of glycodelin expression in the glandular epithelium. Thes e results indicate that blocking the action of progesterone on the endometr ium even for a short period of time has a profound effect on the hCG-induce d response in stromal fibroblasts, In contrast, for the diminution of gland ular epithelial function in the presence of an ovary requires prolonged inh ibition of progesterone action, suggesting a potential paracrine effect on the endometrium from the Ct in response to hCG.