Estrogen and progesterone receptors in the endometrium

The endometrium, as a target of estrogens and progestins, possesses the respective receptor proteins. These receptors belong to the superfamily of nuclear receptors, having important functional domains required for steroid ligand binding, for dimer formation, for interaction with HREs of DNA, for transcription modulation, for association with other proteins, for intracellular trafficking, and other activities. The mechanism of action of the steroid hormones involves modulation of gene activity through interaction of the hormone-receptor complex with HREs and with other nuclear proteins, but also encompasses nongenomic effects, which accounts for the rapid effects of the steroids on cellular functions. Antihormones-antiestrogen and antiprogestins-compete with their respective hormones for binding sites on the receptor molecules. Some antihormones are partial agonists. The molecular mechanisms underlying the dual behavior of antihormones is under consideration. The concentration of ER and PR in different physiological and pathophysiological states, such as the menstrual cycle, pregnancy, and endometrial cancer, has been determined by biochemical and immuno(cyto)chemical methods. The levels of estrogens and progestins are important regulators of ER and PR gene expression. Estradiol acts as a cell mitogen, inducing key genes involved in replication, and its tumor promoter effect is discussed in this sense, whereas progesterone has reverse effects when compared to estradiol and acts as a differentiation factor. The cross-talk between the endocrine system, growth factors, and neurotransmitters can take place both at the receptor level, involving mainly phosphorylation reactions, and at the gene level, mainly through protein-protein interactions.