Expression of Nuclear Receptor Coactivators in the Brain of Progestin Receptor Isoform-specific Knock-out Mice

The ovarian steroid hormones estradiol (E) and progesterone (P) play important roles in reproductive physiology and behavior. The effects of E and P are mediated by their respective receptors, estrogen receptor (ER) and progestin receptor (PR) which function as transcription factors. PR is expressed as two isoforms, full length PR-B and the N-terminally truncated PR-A, by the induction of E in reproductively-relevant brain regions, including the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus (ARC), and medial preoptic area (MPOA). These two PR isoforms, PR-A and PR-B, have profound functional differences in physiology and behavior. Findings from our lab and others have shown that members of a family of steroid receptor coactivators (SRCs), SRC-1 and SRC-2, facilitate the ER-mediated transactivation of the PR gene in the hypothalamus and in ERand PR-dependent reproductive behaviors in female rodents. To understand the expression patterns of SRC-1 and SRC-2 with PR-A and PR-B, we investigated whether SRC-1 or SRC-2 are differentially expressed with the PR isoforms in PR-A knock-out (PRAKO) and PR-B knock-out (PRBKO) mice brain. We used triple label immunohistochemistry in ovariectomized PR transgenic isoform-specific knock-out mice brain and visualized SRC-1, SRC-2 and PR isoform immunoreactive cells by confocal microscopy. SRC-1 and SRC-2 immunoreactive cells were detected in the VMN, ARC, and MPOA of both PRAKO and PRBKO mice. The results of our study bring us closer to understanding how steroid receptor coactivators contribute to the alternative transcription of distinct E-inducible promoters of the two PR isoforms.