ABSTRACT
The ovarian steroid hormone progesterone (P4) is a critical regulator of reproductive events associated with all aspects of the establishment and maintenance of pregnancy. Well-characterized functions of P4 include regulating uterine receptivity for blastocyst attachment, controlling the progression of uterine and embryonic interactions, inducing stromal cell differentiation, and regulating epithelial cell proliferation. Most of the physiological affects of P4 are mediated through its receptor, the progesterone receptor (PGR). PGR is a transcription factor that belongs to the nuclear receptor superfamily. This superfamily represents the largest family of transcription factors that share structural similarities and key functional domains.1,2 The three major functional domains of PGR, like all nuclear receptors, are the ligand-binding domain (LBD), the DNA-binding domain (DBD), and an activation domain (AF).The LBD confers specificity to the receptor for a particular ligand or molecule that regulates its transcriptional activation. The DBD determines which DNA sequences the receptor will recognize, while the AFs link the transcriptional activity of the receptors to the core transcriptional complexes.3 As shown in Figure 13.1, PGR is encoded in one gene and exists as several isoforms with the most well characterized being PRA, PRB, and PRC. These isoforms arise from the alternate translation start sites in the PGR gene. The human PRA isoform differs from the PRB isoform in that it lacks the first 164 amino acids contained in PRB, whereas the PRC isoform contains a truncated DBD and a full-length LBD.4
