Russell J, Lettieri D, Adler J, Sherwood L M
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Mol Endocrinol. 1990 Mar;4(3):505-9. doi: 10.1210/mend-4-3-505.
Previous studies have shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] decreases levels of mRNA for prepro-PTH as well as PTH secretion after chronic exposure (24-48 h) of parathyroid cells in tissue culture. We have now extended these studies to determine the effects of the vitamin D3 metabolite on parathyroid secretory protein (PSP) gene expression. Primary cultures of bovine parathyroid cells were incubated with 10(-8) M 1,25-(OH)2D3 for periods of time ranging from 24-72 h. As observed in earlier experiments, prepro-PTH mRNA decreased to less than 50% of the control value after 72 h. In marked contrast, PSP mRNA showed a 2.5-fold increase by 24 h and greater than 7-fold stimulation by 72 h. In the same studies, PTH secretion was suppressed (to 60% of control), while PSP secretion was increased by 40% over control values. Exposure to high (2.5 mM) or low (0.5 mM) calcium had no effect on PSP mRNA, even though low calcium stimulated the secretion of PSP while high calcium suppressed secretion. These studies showed that 1,25-(OH)2D3 has opposite effects on the gene expression of PSP and PTH in bovine parathyroid cells in tissue culture.
先前的研究表明,在组织培养中对甲状旁腺细胞进行慢性暴露(24 - 48小时)后,1,25 - 二羟基维生素D3 [1,25-(OH)2D3]可降低前甲状旁腺素原(prepro - PTH)的mRNA水平以及甲状旁腺激素(PTH)的分泌。我们现在扩展了这些研究,以确定维生素D3代谢产物对甲状旁腺分泌蛋白(PSP)基因表达的影响。将牛甲状旁腺细胞原代培养物与10(-8) M的1,25-(OH)2D3孵育24至72小时。正如在早期实验中所观察到的,72小时后前甲状旁腺素原mRNA降至对照值的50%以下。与之形成鲜明对比的是,PSP mRNA在24小时时增加了2.5倍,在72小时时受到的刺激超过7倍。在同一研究中,PTH分泌受到抑制(降至对照值的60%),而PSP分泌比对照值增加了40%。暴露于高钙(2.5 mM)或低钙(0.5 mM)对PSP mRNA没有影响,尽管低钙刺激了PSP的分泌而高钙抑制了分泌。这些研究表明,在组织培养中,1,25-(OH)2D3对牛甲状旁腺细胞中PSP和PTH的基因表达具有相反的作用。