ABSTRACT
INTRODUCTION: ENDOMETRIAL CANCER AND THE LINK TO STEROID HORMONES AND STEROID RECEPTORS
Endometrial carcinogenesis is related to overexposure to estrogen that is not modulated by the differentiating effects of progesterone and potentially other steroid hormones including
androgens and glucocorticoids. The endometrium is one of the most estrogen-sensitive tissues in the body and responds to estrogens with rapid cell growth: Unopposed estrogen stimulation can lead to endometrial hyperplasia, cellular atypia, and endometrial cancer. Initial studies indicating that the proliferation of the endometrium was under hormonal control employed tritiated thymidine incorporation as a measure of DNA synthesis in animal models. These original data have now been supplemented by detailed investigations that show that estrogens act upon the endometrium through estrogen receptors (ERs) resulting in the induction of growth factors such as the epidermal growth factor (EGF) (1), its receptor (EGFR) (2), insulin-like growth factor-1 (IGF-1) (3), and growth-enhancing protooncogenes, such as c-fos and c-myc (4). ERs induce progesterone receptors (PRs) through which progesterone exerts differentiating effects on the glandular epithelium and opposes the growth-promoting effects of estrogen. Androgen receptors (ARs) and glucocorticoid receptors (GRs) are also expressed in the endometrium and in endometrial tumors and may be involved in endometrial differentiation (5,6).
