Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Biochem Biophys Res Commun. 2011 Apr 15;407(3):472-8. doi: 10.1016/j.bbrc.2011.03.037. Epub 2011 Mar 21.
Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.
甲状旁腺激素相关蛋白 (PTHrP) 水平升高是导致恶性肿瘤所致高钙血症 (HHM) 的原因，这在治疗终末期恶性肿瘤患者方面具有重要的临床意义。甾体激素已知可抑制 PTHrP 的表达。然而，缺乏将多种甾体激素与 PTHrP 表达联系起来的详细研究。在此，我们研究了甾体激素对四种高 PTHrP 产生细胞系中 PTHrP 表达的影响。我们的研究确立了甾体激素可负性调节 PTHrP 的表达。维生素 D 受体、雌激素受体 α、糖皮质激素受体和孕激素受体对于相应配体抑制 PTHrP 表达是必需的。一个显著的例外是雄激素受体，其在雄激素处理的细胞中抑制 PTHrP 表达是可有可无的。我们提出了一条（多条）涉及核受体的通路来抑制 PTHrP 的表达。
