Mechanisms of the Progestational Regulation
In humans, progesterone stimulation of the estradiol-primed endometrium initiates decidualization of the stromal cells around the spiral arterioles to establish the decidual cell as a major cell type of the secretory phase and pregnant endometrium. Prior studies from our laboratory have established that progestins stimulate the endometrial decidual/ stromal expression of two crucial modulators of hemostasis: tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1). Neither one of these genes contains consensus estrogen or progesterone response elements My studies focused on the mechanisms underlying the enhanced expression by progestin of TF and PAI-1 in vivo as well as in primary human endometrial stromal cell cultures. It was determined that the prolonged progestational upregulation occurred at the transcriptional level. Transient transfections of human endometrial stromal cells were carried out with truncated TF or PAI-1 promoters as well as promoters undergoing site directed mutagenesis.