Steroid Receptor Coregulators Can Modulate the Action of Progesterone Receptor during the Estrous Cycle in Cow Endometrium

SIMPLE SUMMARY: Proper functioning of the endometrium is necessary for the implantation of the embryo after fertilization and its development throughout pregnancy. The key role in this process plays appropriate action of progesterone through the nuclear receptor isoforms. The action of the receptor is regulated by the attachment of receptor modulators called coregulators which include coactivators and corepressors. Their improper expression in humans causes a malfunction of progesterone receptors and leads to disorders of pregnancy. However, in farm animals, such disorders may be one of the reasons leading up to early embryonic lethality, which in cows reaches up to 40%. Obtained results indicate the important role of the studied coregulators in regulating progesterone activity in endometrial cells, especially during the preimplantation period. Therefore, they can be helpful in better understanding the regulation and expression of the coactivators and corepressors in cow endometrium during the estrous cycle and can contribute to reducing this problem. They can also be of significant practical importance, making for the increased efficiency of breeding these animals. ABSTRACT: Nuclear receptor coregulators include coactivators and corepressors which associate with the progesterone receptor (PGR) during its activation. Fluctuations in the transcription levels of their respective genes and subsequent protein production as well as in related activities for histone acetyltransferase (HAT) and histone deacetylase (HDAC) can affect PGR function and thus change the action of progesterone (P4) in bovine endometrium during the estrous cycle. Endometrial tissue on days 2–5, 6–10, 11–16, and 17–20 of the estrous cycle was used for determination of the mRNA expression levels of coactivators P300, CREB, and SRC-1 along with corepressor NCOR-2 using Real-Time PCR, with protein levels by Western blot. Coregulators cellular localizations were assessed by immunohistochemistry whereas the activities of HAT and HDAC by using EIA. The highest levels of mRNA and proteins for all of the investigated coregulators, as well as the highest levels of activity for HAT and HDAC, were detected over days 2–16 of the estrous cycle. All of the tested coregulatory proteins were localized in the nuclei of endometrial cells. This research indicates the important role of coregulators of the PGR receptor in regulating P4 activity in endometrial cells, especially during the pre-implantation period.