Cyclic Changes in the Expression of p57(kip2) in Human Endometrium and its Regulation by Steroid Hormones in Endometrial Stromal Cells In Vitro

Abstract

We investigated the expressions of p57(kip2) and p27(kip) and its regulation by steroids in the normal and abnormal human endometrium. Endometrial p27(kip1) and p57(kip2) messenger RNA (mRNA) were markedly increased in the secretory phase. P57(kip2) protein was absent in proliferative phase but appeared in glandular epithelium together with early-to mid-secretory phase stromal cells. During the late secretory phase, strong p57(kip2) protein immunoreactivity was found in the stromal cells. In both endometrial hyperplasia and cancer, the expression of p57(kip2) protein was low. In cultured human endometrial stromal cells (ESCs), p27(kip1) mRNA levels were increased together with the decidual marker prolactin (prl), following treatment with 17 beta-estradiol (E2) and progesterone (P4). At 1 nmol/L, the glucocorticoid receptor (GR) agonist dexamethasone (DEX) induced prl, p57(kip2), and p27(kip1) mRNA in ESCs. Taken together, upregulation of p57(kip2) may play an important role in the decidual differentiation by P4 and growth inhibition of malignant cells in human endometrium.