Breton C, Neculcea J, Zingg H H
Laboratory of Molecular Endocrinolog, Royal Victoria Hospital, Montreal, Québec, Canada.
Endocrinology. 1996 Jul;137(7):2711-7. doi: 10.1210/endo.137.7.8770890.
Although the neurohypophyseal hormone oxytocin (OT) is best know for its role in reproduction, OT also stimulates natriuresis at physiological plasma levels. This effect is mediated via specific renal OT receptors (OTRs). In the present study, we have characterized rat renal OTR gene transcripts and assessed their regulation during gestation and in response to gonadal steroid treatment. Using a specific rat OTR probe, two major OTR messenger RNA (mRNA) bands [6.7 and 4.8 kilobases (kb)] were detected in renal extracts, corresponding to two of the three bands present in rat uterus. In contrast to the dramatic rise of OTR mRNA levels at term in the uterus and pituitary, renal OTR mRNA levels underwent a strong more than 3-fold decrease at term. Binding studies using a iodinated specific OT antagonist revealed a concomitant decrease in renal OT-binding sites. On the other hand, estrogen (E2) treatment led to an increase in renal OTR mRNA levels, as is also the case in the uterus and pituitary. However, the predominant E2-induced mRNA species were shorter (3.6 and 3.2 kb) than those present in control rat kidneys (6.7 and 4.8 kb). Analysis by reverse transcriptase-PCR and 5'- and 3'-directed complementary DNA probes indicated that the E2-induced OTR mRNA transcripts possessed the same coding region, but contained a shortened 3'-untranslated region. Binding studies showed that E2 treatment also led to an increase in renal OT-binding sites, suggesting that the shortened OTR transcripts encoded a functional receptor. The present study indicates that the uterine-type OTR gene is expressed in rat kidneys, but that the mechanisms controlling the expression of this gene in the two tissues are markedly different. The differential tissue-specific regulation of OTR gene expression may represent a mechanism by which circulating OT can assume a multifunctional role in both reproduction and sodium homeostasis.
尽管神经垂体激素催产素（OT）因在生殖过程中的作用而最为人熟知，但OT在生理血浆水平时也会刺激利钠作用。这种效应是通过特异性肾OT受体（OTR）介导的。在本研究中，我们已对大鼠肾OTR基因转录本进行了特征分析，并评估了它们在妊娠期间以及对性腺类固醇治疗的反应中的调控情况。使用特异性大鼠OTR探针，在肾提取物中检测到两条主要的OTR信使核糖核酸（mRNA）条带[6.7和4.8千碱基（kb）]，这与大鼠子宫中存在的三条条带中的两条相对应。与子宫和垂体中足月时OTR mRNA水平的急剧升高相反，肾OTR mRNA水平在足月时大幅下降了3倍多。使用碘化特异性OT拮抗剂进行的结合研究显示，肾OT结合位点也随之减少。另一方面，雌激素（E2）处理导致肾OTR mRNA水平升高，子宫和垂体中也是如此。然而，E2诱导的主要mRNA种类比对照大鼠肾脏中的种类短（3.6和3.2 kb）。通过逆转录聚合酶链反应以及5'和3'定向互补DNA探针分析表明，E2诱导的OTR mRNA转录本具有相同的编码区，但包含缩短的3'非翻译区。结合研究表明，E2处理还导致肾OT结合位点增加，这表明缩短的OTR转录本编码了一种功能性受体。本研究表明，子宫型OTR基因在大鼠肾脏中表达，但控制该基因在这两种组织中表达的机制明显不同。OTR基因表达的差异组织特异性调控可能代表了一种机制，通过该机制循环中的OT可以在生殖和钠稳态中发挥多功能作用。
