PARATHYROID-HORMONE GENE-EXPRESSION IN HYPOPHOSPHATEMIC RATS

Phosphate is central to bone metabolism and we have therefore studied whether parathyroid hormone (PTH) is regulated by dietary phosphate in vivo. Weanling rats were fed diets with different phosphate contents for 3 wk: low phosphate (0.02%), normal calcium (0.6%), normal phospha te (0.3%),and calcium (0.6%); high phosphate( 1.2%), high calcium (1.2 %), The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)(2)D-3 together with decreased PTH mRNA level s (25+/-8% of controls, P < 0.01) and serum immunoreactive PTH (4.7+/- 0.8: 22.1+/-3.7 pg/ml; low phosphate: control, P < 0.05). A high phosp hate diet led to increased PTH mRNA levels. In situ hybridization show ed that hypophosphatemia decreased PTH mRNA in all the parathyroid cel ls. To separate the effect of low phosphate from changes in calcium an d vitamin D rats were fed diets to maintain them as vitamin D-deficien t and normocalcemic despite the hypophosphatemia. Hypophosphatemic, no rmocalemic rats with normal serum 1,25(OH)(2)D-3 levels still had decr eased PTH mRNAs. Nuclear transcript run-ons showed that the effect of low phosphate was posttranscriptional. Calcium and 1,25(OH)(2)D-3 regu late the parathyroid and we now show that dietary phosphate also regul ates the parathyroid by a mechanism which remains to be defined.