Secondary hyperparathyroidism is a frequent complication of chronic renal f
ailure resulting in severe bone disease. Secondary hyperparathyroidism is c
om posed of increased in parathyroid hormone (PTH) synthesis and secretion
due to an increase in PTH gene expression and parathyroid cell proliferatio
n. PTH gene expression is regulated by calcium, phosphate and 1,25-dihydrox
y vitamin D (1,25(OH)(2)D). 1,25(OH)(2)D-3 injected to rats leads to a dram
atic decrease in PTH gene transcription without any increase in serum calci
um. Hypocalcemia leads to a large increase in PTH mRNA levels which is post
-transcriptional. Hypophosphatemia leads to a marked decrease in PTH gene e
xpression that is also post-transcriptional. The mechanisms of the post-tra
nscriptional effects of calcium and phosphate on the PTH gene have shown to
be due to changes in protein-RNA interactions at the PTH mRNA 3'-UTR. Hypo
calcemia leads to increased binding of parathyroid cytosolic proteins to th
e PTH mRNA 3'-UTR and hypophosphatemia to decreased binding of these protei
ns to the PTH mRNA 3'-UTR. The binding of the parathyroid proteins stabiliz
es the PTH RNA in an in vitro degradation assay. In rats with experimental
uremia due to 5/6 nephrectomy, there is an increase in PTH mRNA levels due
to a decrease in degradation of the PTH RNA as determined by this assay. Th
e characterization of the parathyroid cytosolic proteins that interact with
the PTH mRNA 3'-UTR may lead to a clearer understanding of how changes in
serum calcium and phosphate result in secondary hyperparathyroidism.