Progesterone inhibits cytokine/TNF-α production by porcine CL macrophages via the genomic progesterone receptor

Abstract In the pig, luteolytic sensitivity to PGF-2α (=LS) is delayed until D.13 of the estrous cycle. While the control of LS is unknown, it is temporally associated with macrophage (MAC; which secrete TNF-α) infiltration into the CL, and previous studies have shown that TNF-α induces LS in porcine luteal cells (LC) in culture. This study was designed to explore the control of LS by CL MAC/TNF-α by Progesterone (P4), and to examine the hypothesis that P4 acting via the genomic P4 receptor (PGR), inhibits CL MAC TNF-α and thus plays a key role in regulating LS during the pig estrous cycle. In Experiment 1, the effects of LC on CL MAC cytokine/TNF-α mRNA expression in co-culture were examined (MID cycle; ∼D.7-12; no LS); results showed that LC was inhibitory to cytokine/TNF-α. In Expt. 2, the effects of P4 or R5020 (PGR-agonist) on CL MAC cytokine/TNF-α mRNA expression were examined (MID cycle; ∼D.7-12; no LS); results showed that both P4 and R5020 dose-dependently inhibited TNF-α. In Expt. 3, CL MAC were isolated from CL at MID (∼D.7-12; no LS) and LATE (∼D.13-18; + LS) cycle, and TNF-α/PGR mRNA measured. Results indicated that while TNF-α mRNA was 4.2-fold greater in CL MAC from LATE vs. MID cycle, PGR mRNA was 4.5-fold greater in CL MAC from MID vs. LATE cycle. These data support our hypothesis and suggest that progesterone, acting via PGR, plays a critical physiological role in the control of TNF-α production by CL MAC and LS during the pig estrous cycle.