MacDonald P N, Ritter C, Brown A J, Slatopolsky E
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
J Clin Invest. 1994 Feb;93(2):725-30. doi: 10.1172/JCI117026.
1,25-dihydroxyvitamin D3[1,25(OH)2D3] suppresses parathyroid hormone (PTH) gene transcription. Recent evidence suggests that retinoid X receptors are involved in 1,25(OH)2D3-mediated transcriptional events. However, little data exists for a role of retinoids in parathyroid function or in PTH expression. In the present study, we observed that all-trans- or 9-cis retinoic acid suppressed the release of PTH from bovine parathyroid cell cultures. Both retinoids were remarkably potent with significant decreases evident at 10(-10) M and a maximally suppressive effect (approximately 65%) at 10(-7) M. All-trans-retinol was considerably less potent in this system. The effect was not evident until 12 h, suggesting that retinoids did not affect the rapid secretion of preexisting PTH stores. PreproPTH mRNA levels were also suppressed by retinoic acid and the retinoid potencies were similar to those observed in the secretion studies. Combined treatment with 10(-6) M retinoic acid and 10(-8) M 1,25(OH)2D3 more effectively decreased PTH secretion and preproPTH mRNA than did either compound alone. These data indicate that retinoic acid: (a) elicits a bioresponse in bovine parathyroid cells; (b) attenuates PTH expression at the protein and mRNA levels, and (c) acts independently of 1,25(OH)2D3 in the control of PTH expression.
1,25 - 二羟基维生素D3[1,25(OH)2D3]可抑制甲状旁腺激素（PTH）基因转录。最近的证据表明，维甲酸X受体参与了1,25(OH)2D3介导的转录事件。然而，关于类维生素A在甲状旁腺功能或PTH表达中的作用的数据很少。在本研究中，我们观察到全反式或9 - 顺式视黄酸可抑制牛甲状旁腺细胞培养物中PTH的释放。两种类维生素A都具有显著的效力，在10(-10) M时明显降低，在10(-7) M时具有最大抑制作用（约65%）。在该系统中，全反式视黄醇的效力要低得多。这种作用直到12小时才明显，这表明类维生素A并不影响预先存在的PTH储存的快速分泌。前甲状旁腺素原（PreproPTH）mRNA水平也受到视黄酸的抑制，且类维生素A的效力与分泌研究中观察到的相似。与单独使用任何一种化合物相比，联合使用10(-6) M视黄酸和10(-8) M 1,25(OH)2D3能更有效地降低PTH分泌和PreproPTH mRNA水平。这些数据表明，视黄酸：（a）在牛甲状旁腺细胞中引发生物反应；（b）在蛋白质和mRNA水平上减弱PTH表达；（c）在PTH表达的控制中独立于1,25(OH)2D3发挥作用。
