Molecular and Cellular Biology of Mammalian Progesterone Receptors

Publisher Summary Synthesis of high specific activity tritiated steroids has allowed the study of their fate in target organs at concentrations at which they elicit specific physiological responses. This approach has led to the discovery of estrogen receptors (ERs). This chapter reviews that extensive analyses of the steroid-binding specificity of receptors in various species were undertaken. Initial experiments were performed using guinea pig uterus as a model, and it was established that ovariectomized animals had a low but measurable level of receptor which increased after estrogen administration. It also discusses that use of actinomycin D and cycloheximide suggested these changes were because of messenger RNA (mRNA) induction and protein synthesis. It also presents that progesterone down-regulated its own receptor. These results were later extended to various species including human and various cell types such as the extensively studied breast cancer cell lines. The chapter describes these regulatory mechanisms in a model system, which is tested in a physiological situation, by measuring receptor levels in the uterus during the estrous cycle.