which are contained within a larger region important for ligand binding and for receptor dimerization. Upon activation, the receptors dimerize, bind to specific DNA sequences termed steroid response elements, and activate the transcription of target genes. Typically, the activation of receptors is studied by using artificial target genes on plasmids that contain one or more of the specific response elements placed 5' of a promoter and a cDNA for an enzyme such as chloramphenicol acetyl-transferase which can be easily assayed (Denner et al., 1990b). The activity of the receptor can then be studied by transfecting the reporter gene (and a plasmid that expresses receptor if necessary) into a target cell, treating with the desired agonist or antagonist, and measuring the resulting enzyme activity. Although there are many similarities in the mechanisms of action of the various steroid receptors, there are also significant differences. The structure and function of the human progesterone receptor are described below.
The human progesterone receptor is expressed as two forms, hPR-B and hPR-A. Both are derived from the same gene, but are produced from different mRNAs (Kastner et al., 1990). The PR-A is essentially a truncated version of the PR-B lacking the 164 amino terminal amino acids (Figure B2.2). These receptor forms share common hormone binding and DNA binding domains. Either form can activate transcription of a target gene in cells co-transfected with the corresponding expression vector for PR-A or PR-B, as well as a suitable reporter plasmid (Bocquel et al., 1989). However, the two forms differ in their relative activities, depending upon the target gene studied (Bocquel et al., 1989). In the cases examined thus far, both forms are expressed in cells and in tissues that contain progesterone receptor (Horwitz and Alexander, 1983; Lessey et al., 1983; Feil et al., 1988). Although it is presumed that both forms exist in the same cells, this has not been unequivocally demonstrated.