Effect of Steroid Hormones, Prostaglandins (E2 and F2α), Oxytocin, and Tumor Necrosis Factor Alpha on Membrane Progesterone (P4) Receptors Gene Expression in Bovine Myometrial Cells

SIMPLE SUMMARY: The myometrium is one of the layers of the uterus. It consists of smooth muscle and can therefore stretch during pregnancy and contract during parturition. Thus, it can assist oocyte fertilization and its transport in the fallopian tube as well as the blastocyst implantation process. Myometrial function is regulated by the activation of several signal transduction pathways and the expression of many genes. Among them are non-genomic membrane progesterone (P4) receptors such as progesterone receptor membrane components (PGRMC) 1 and 2 and membrane progestin receptors (mPR) alpha (mPRα), beta (mPRβ), and gamma (mPRγ). Their improper action may cause disturbances in fertilization and the correct course of the estrous cycle and pregnancy. The results of this study indicate the possible role of P4, estradiol (E2), prostaglandins (PG) E2 and F2α, oxytocin (OT), and tumor necrosis factor alpha (TNFα) in the regulation of membrane P4 receptor gene expression. This suggests that the local hormonal milieu may influence the activity of these receptors and P4 action in myometrial cells during the estrous cycle. Therefore, elucidation of the mechanisms by which the action of membrane P4 receptors in the myometrium is regulated may be an important element in understanding the proper functioning of the uterus and can help to reduce abnormalities in the course of pregnancy in cows. ABSTRACT: Myometrium tissue shows the expression of non-genomic membrane progesterone (P4) receptors, such as progesterone receptor membrane components (PGRMC) 1 and 2 and membrane progestin receptors (mPR) alpha (mPRα), beta (mPRβ), and gamma (mPRγ). Their variable expression in the bovine uterus during the estrous cycle and early pregnancy suggests that ovarian steroids and luteotropic and/or luteolytic factors may regulate the expression of these receptors in the myometrium. Therefore, this study aimed to examine the effect of P4, estradiol (E2), P4 with E2, prostaglandins (PG) E2 and F2α, oxytocin (OT), and tumor necrosis factor α (TNFα) on the gene expression of PGRMC1, PGRMC2, serpine-1 mRNA-binding protein (SERBP1), and mPRα, mPRβ, and mPRγ in bovine myometrial cells from days 6 to 10 and 11 to 16 of the estrous cycle. The PGE2 concentration and mRNA expression were determined by EIA and real-time PCR, respectively. The data indicated that P4 and E2 can affect the mRNA expression of all studied receptors and SERPB1. However, PGE2, OT, and TNFα could only modulate the expression of PGRMC1, PGRMC2, and SERPB1, respectively. Steroids/factors changed the expression of PGRMC and mPR genes depending on the dose, the stage of the estrous cycle, and the types of receptors. This suggests that the local hormonal milieu may influence the activity of these receptors and P4 action in myometrial cells during the estrous cycle.