Stites D P, Siiteri P K
Immunol Rev. 1983;75:117-38. doi: 10.1111/j.1600-065x.1983.tb01093.x.
In considering the potential of known reproductive hormones to act as immunoregulatory substances during pregnancy, progesterone clearly is an attractive candidate for the following reasons: 1) progesterone is a primitive hormone occurring in virtually all species; 2) it is the only hormone which has been shown to be absolutely essential for maintenance of pregnancy in a variety of mammals, including the human; 3) it has demonstrable in vivo and in vitro immunosuppressive effects when present in concentrations known to be present in the human placenta; 4) it has weak systemic effects compared to cortisol; 5) in many species including primates, it is produced by trophoblastic cells: potential targets of the maternal immune system. Inhibitory effects of progesterone on immune cells have been demonstrated despite the absence of classical steroid receptors for progesterone (Lippman 1979). Specific functions of human T-lymphocytes and macrophages are inhibited by concentrations of progesterone known to occur in the placenta (10(-6)-10(-5) M). Although similar effects are produced by cortisol, clear-cut differences exist in the mechanisms by which cortisol and progesterone act on immune cells. The results suggest, but do not prove, that progesterone does not act on immune cells by binding to the glucocorticoid receptor. This can be considered to be advantageous, for otherwise pregnancy could be associated with glucocorticoid toxicity. Remarkable local anti-inflammatory activity of progesterone has been observed in vivo, although the mechanism of this effect is poorly understood. The striking absence of inflammatory cells in the pregnant uterus until a few days before birth is consistent with known effects of progesterone from animal studies. Whether this regulatory effect on cell traffic is exerted directly by progesterone or by secondary mediators produced within the uterus remains to be determined. In either case, appropriate timing of the removal of progesterone's influence may constitute an integral part of the process of parturition. Post-partum resolution of the placental attachment-site has many of the cellular characteristics of transplant rejection. Furthermore, it has recently been proposed that inflammatory cells which invade the cervix may generate prostaglandins which mediate the biochemical changes that are essential for its dilation to allow escape of the fetus (Liggins 1981). If the processes begin prior to delivery as a consequence either of progesterone withdrawal or inhibition of its activity, parturition may in fact be considered as a delayed rejection process.(ABSTRACT TRUNCATED AT 400 WORDS)
在考虑已知生殖激素在孕期作为免疫调节物质的潜力时，孕酮显然是一个有吸引力的候选者，原因如下：1）孕酮是一种几乎存在于所有物种中的原始激素；2）它是唯一已被证明对包括人类在内的多种哺乳动物维持妊娠绝对必要的激素；3）当以已知存在于人类胎盘的浓度存在时，它具有可证明的体内和体外免疫抑制作用；4）与皮质醇相比，它的全身作用较弱；5）在包括灵长类动物在内的许多物种中，它由滋养层细胞产生：滋养层细胞是母体免疫系统的潜在靶点。尽管缺乏孕酮的经典类固醇受体，但孕酮对免疫细胞的抑制作用已得到证实（Lippman，1979年）。已知胎盘内存在的孕酮浓度（10⁻⁶ - 10⁻⁵ M）会抑制人类T淋巴细胞和巨噬细胞的特定功能。虽然皮质醇也会产生类似的效果，但皮质醇和孕酮作用于免疫细胞的机制存在明显差异。结果表明，但未证明，孕酮不是通过与糖皮质激素受体结合来作用于免疫细胞的。这可以被认为是有利的，否则妊娠可能与糖皮质激素毒性有关。虽然对这种作用的机制了解甚少，但在体内已观察到孕酮具有显著的局部抗炎活性。直到出生前几天，妊娠子宫中明显缺乏炎性细胞，这与动物研究中已知的孕酮作用一致。这种对细胞运输的调节作用是由孕酮直接发挥的，还是由子宫内产生的次级介质介导的，仍有待确定。无论哪种情况，适时消除孕酮的影响可能是分娩过程不可或缺的一部分。产后胎盘附着部位的消退具有许多移植排斥的细胞特征。此外，最近有人提出，侵入子宫颈的炎性细胞可能产生前列腺素，这些前列腺素介导子宫颈扩张以允许胎儿娩出所必需的生化变化（Liggins，1981年）。如果由于孕酮撤退或其活性受到抑制，这些过程在分娩前就开始，那么分娩实际上可能被视为一个延迟的排斥过程。（摘要截至于400字）
