Department of Animal Science, Texas A&M University, College Station, Texas, USA.
Biol Reprod. 2010 Jan;82(1):35-43. doi: 10.1095/biolreprod.109.079608. Epub 2009 Aug 19.
Establishment of pregnancy in ruminants requires conceptus elongation and production of interferon tau (IFNT), the pregnancy recognition signal that maintains the corpus luteum and progesterone (P4) secretion. The enzymes hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) and HSD11B2 catalyze the interconversion of inactive cortisone and active cortisol, which is a biologically active glucorticoid and ligand for the receptor subfamily 3, group C, member 1 (glucocorticoid receptor) (NR3C1). The activity of HSD11B1 is stimulated by P4, prostaglandins, and cortisol. These studies determined the effects of pregnancy, P4, and IFNT on HSD11B1, HSD11B2, prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (PTGS2), and nuclear NR3C1 in the ovine uterus. Endometrial HSD11B1 mRNA levels were more abundant between Days 12 and 16 of pregnancy than the estrous cycle, and HSD11B1 and PTGS2 expression in the endometrial luminal and superficial glandular epithelia was coincident with conceptus elongation. HSD11B1 mRNA was very low in the conceptus, whereas HSD11B2 mRNA was abundant in the conceptus but not in the uterus. Treatment of ewes with P4 induced, and intrauterine infusions of IFNT modestly stimulated, HSD11B1 expression in the endometrial luminal and superficial glandular epithelia. In all of the studies, HSD11B1 and PTGS2 expression was coincident in the endometrial epithelia, and NR3C1 was present in all endometrial cell types. Collectively, these results support hypotheses that endometrial epithelial HSD11B1 expression is induced by P4 as well as stimulated by IFNT and PTGS2-derived prostaglandins and that HSD11B1-regenerated cortisol acts via NR3C1 to regulate ovine endometrial functions during early pregnancy.
在反刍动物中，妊娠的建立需要胚胎伸长和干扰素 tau（IFNT）的产生，IFNT 是维持黄体和孕酮（P4）分泌的妊娠识别信号。羟甾体（11-β）脱氢酶 1（HSD11B1）和 HSD11B2 这两种酶可催化无活性的可的松和活性皮质醇的相互转化，皮质醇是一种生物活性的糖皮质激素，也是受体亚家族 3、C 组、成员 1（糖皮质激素受体）（NR3C1）的配体。HSD11B1 的活性受到 P4、前列腺素和皮质醇的刺激。这些研究确定了妊娠、P4 和 IFNT 对绵羊子宫中 HSD11B1、HSD11B2、前列腺素内过氧化物合酶 2（前列腺素 G/H 合酶和环加氧酶）（PTGS2）和核 NR3C1 的影响。妊娠第 12 至 16 天的子宫内膜 HSD11B1mRNA 水平比发情周期更为丰富，并且子宫内膜腔和浅层腺上皮中的 HSD11B1 和 PTGS2 表达与胚胎伸长同时发生。胚胎中 HSD11B1mRNA 的含量非常低，而 HSD11B2mRNA 在胚胎中丰富，但在子宫中不存在。用 P4 处理母羊会诱导子宫内膜腔和浅层腺上皮中 HSD11B1 的表达，而宫内 IFNT 输注则适度刺激 HSD11B1 的表达。在所有研究中，HSD11B1 和 PTGS2 的表达在子宫内膜上皮中同时发生，并且 NR3C1 存在于所有子宫内膜细胞类型中。综上所述，这些结果支持以下假设，即子宫内膜上皮细胞 HSD11B1 的表达是由 P4 诱导的，同时也受到 IFNT 和 PTGS2 衍生的前列腺素的刺激，而 HSD11B1 再生的皮质醇通过 NR3C1 作用于绵羊子宫内膜功能，从而调节妊娠早期的功能。
