Spencer T E, Bazer F W
Department of Animal Science, Texas A & M University, College Station, TX 77843-2471, USA.
Endocrinology. 1996 Mar;137(3):1144-7. doi: 10.1210/endo.137.3.8603586.
Tau interferons (IFNtau) are a unique subclass of the omega interferons that are transiently produced by the trophectoderm of the conceptus (embryo and associated membranes) during early pregnancy in ruminants. IFNtau acts as an antiestrogen on the endometrium to suppress increases in estrogen receptor (ER) and oxytocin receptor (OTR) gene expression which prevents pulsatile production of prostaglandin F2alpha and regression of the corpus luteum or luteolysis. In this study, steady-state levels of ER mRNA and transcription rates of the ER and OTR genes were two-fold lower in the endometrium of pregnant as compared to cyclic ewes on day 15. Levels of ER mRNA and ER and OTR gene transcription were also two-fold lower in the endometrium of day 15 cyclic ewes receiving intrauterine injections of recombinant ovine IFNtau from day 11 to day 14 compared to control ewes. Results suggest that the antiluteolytic action of IFNtau is to suppress transcription of the ER gene by a negative-acting transcriptional mechanism which prevents estrogen-induced increases in OTR gene expression in the endometrium. The novel antiestrogenic effects of IFNtau, combined with its Type I IFN characteristics and low cytotoxicity, suggest that this trophoblast IFN may have potential value as a chemotherapeutic agent for the treatment of infertility, viral disease and estrogen-dependent malignant disorders.
τ干扰素（IFNτ）是ω干扰素的一个独特亚类，在反刍动物怀孕早期由孕体（胚胎及相关胎膜）的滋养外胚层短暂产生。IFNτ在子宫内膜上作为一种抗雌激素发挥作用，抑制雌激素受体（ER）和催产素受体（OTR）基因表达的增加，从而阻止前列腺素F2α的脉冲式产生以及黄体退化或黄体溶解。在本研究中，与第15天的周期性母羊相比，怀孕母羊子宫内膜中ER mRNA的稳态水平以及ER和OTR基因的转录率降低了两倍。与对照母羊相比，在第11天至第14天接受子宫内注射重组羊IFNτ的第15天周期性母羊子宫内膜中，ER mRNA水平以及ER和OTR基因转录也降低了两倍。结果表明，IFNτ的抗黄体溶解作用是通过一种负向作用的转录机制抑制ER基因的转录，从而阻止雌激素诱导的子宫内膜中OTR基因表达增加。IFNτ的新型抗雌激素作用，连同其I型干扰素特性和低细胞毒性，表明这种滋养层干扰素作为治疗不孕症、病毒性疾病和雌激素依赖性恶性疾病的化疗药物可能具有潜在价值。
