Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Domest Anim Endocrinol. 2020 Jul;72:106426. doi: 10.1016/j.domaniend.2019.106426. Epub 2019 Dec 9.
In pigs, 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 secretes tumor necrosis factor [TNF]-α) infiltration into the corpora lutea (CL), and previous studies have shown that TNF-α induces LS in porcine luteal cells (LCs) in culture. This study was designed to explore the control of LS by CL macrophage (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 LCs 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 experiment 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 experiment 3, CL MACs 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 MACs from LATE vs MID cycle, PGR mRNA was 4.5-fold greater in CL MACs 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 MACs and LS during the pig estrous cycle.
在猪中，PGF-2α（=LS）的溶黄体敏感性直到发情周期的第 13 天才变得敏感。虽然 LS 的控制机制尚不清楚，但它与巨噬细胞（MAC；分泌肿瘤坏死因子 [TNF]-α）渗透到黄体（CL）的时间有关，先前的研究表明，TNF-α在培养的猪黄体细胞（LC）中诱导 LS。本研究旨在通过 CL 巨噬细胞（CL MAC）/TNF-α 研究 LS 的控制机制，孕激素（P4），并检验假设，即 P4 通过基因组 P4 受体（PGR）发挥作用抑制 CL MAC TNF-α，并在猪发情周期中对 LS 起关键作用。在实验 1 中，检查了 LC 在共培养中对 CL MAC 细胞因子/TNF-α mRNA 表达的影响（MID 周期；d 7-12；无 LS）；结果表明 LC 对细胞因子/TNF-α具有抑制作用。在实验 2 中，检查了 P4 或 R5020（PGR-激动剂）对 CL MAC 细胞因子/TNF-α mRNA 表达的影响（MID 周期；d 7-12；无 LS）；结果表明 P4 和 R5020 均剂量依赖性地抑制 TNF-α。在实验 3 中，从 MID（d 7-12；无 LS）和 LATE（d 13-18；+ LS）周期的 CL 中分离 CL MAC，并测量 TNF-α/PGR mRNA。结果表明，虽然 LATE 周期 CL MAC 中的 TNF-α mRNA 增加了 4.2 倍，但 MID 周期 CL MAC 中的 PGR mRNA 增加了 4.5 倍。这些数据支持我们的假设，并表明孕激素通过 PGR 发挥关键的生理作用，控制猪发情周期中 CL MAC 产生 TNF-α和 LS。
