Polan M L, Loukides J, Nelson P, Carding S, Diamond M, Walsh A, Bottomly K
Department of Obstetrics and Gynecology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
J Clin Endocrinol Metab. 1989 Dec;69(6):1200-6. doi: 10.1210/jcem-69-6-1200.
The relationship between the endocrine system and immune monokines, such as interleukin-1 (IL-1), is of increasing interest. IL-1, a protein secreted by peripheral monocytes and tissue macrophages, mediates a wide variety of immune responses, and its production appears to be inversely related to the level of gonadal steroids. In this report, we have investigated the relationship between estradiol and progesterone concentrations and the level of IL-1 beta mRNA in cultured human peripheral monocytes and pelvic macrophages. Human peripheral monocytes, isolated during the luteal phase of the menstrual cycle, were activated with lipopolysaccharide (10 micrograms/mL). Cellular RNA was isolated and analyzed by Northern analysis using an 800-basepair IL-1 beta cDNA probe. Hybridization with 32P-labeled probe showed maximal levels of IL-1 beta mRNA occurring between 3 and 7 h of culture. Cultures of lipopolysaccharide-activated human peripheral monocytes incubated for 3-6 h with increasing amounts of progesterone or estradiol (0-10(-5) M) in the presence of either 5% fetal calf serum or 0.1% BSA demonstrated an inverse relationship between IL-1 beta mRNA levels and steroid concentration. In both cases, IL-1 beta mRNA levels decreased by 80-90% as the progesterone concentration increased to 10(-5) M and by 70-90% as the estradiol concentration increased similarly. A similar 80% decrease in IL-1 beta mRNA was observed with peritoneal macrophages incubated with increasing amounts of progesterone. This reciprocal relationship between IL-1 beta mRNA and gonadal steroids may have important ramifications in reproductive biology for both embryonic implantation and fetal survival as well as for clinically relevant changes in bone mass.
内分泌系统与免疫单核因子（如白细胞介素 -1，IL -1）之间的关系越来越受到关注。IL -1是一种由外周单核细胞和组织巨噬细胞分泌的蛋白质，介导多种免疫反应，其产生似乎与性腺类固醇水平呈负相关。在本报告中，我们研究了雌二醇和孕酮浓度与培养的人外周单核细胞及盆腔巨噬细胞中IL -1β mRNA水平之间的关系。在月经周期的黄体期分离出的人外周单核细胞，用脂多糖（10微克/毫升）进行激活。分离细胞RNA并使用800碱基对的IL -1β cDNA探针通过Northern分析进行检测。与32P标记探针的杂交显示，培养3至7小时时IL -1β mRNA水平达到最高。在5%胎牛血清或0.1%牛血清白蛋白存在的情况下，用逐渐增加量的孕酮或雌二醇（0至10^(-5) M）培养脂多糖激活的人外周单核细胞3至6小时，结果显示IL -1β mRNA水平与类固醇浓度呈负相关。在这两种情况下，随着孕酮浓度增加到10^(-5) M，IL -1β mRNA水平下降80%至90%；随着雌二醇浓度类似地增加，IL -1β mRNA水平下降70%至90%。用逐渐增加量的孕酮培养的腹膜巨噬细胞也观察到IL -1β mRNA类似地下降80%。IL -1β mRNA与性腺类固醇之间的这种相互关系可能在生殖生物学中对胚胎着床、胎儿存活以及骨量的临床相关变化都具有重要影响。
