total intracellular PTH was the non-PTH (1-84), most likely A novel mechanism for skeletal resistance in uremia.PTH 7-84. Background. In treating secondary hyperparathyroidism, Conclusion. In patients with chronic renal failure, the presthe target level of serum intact parathyroid hormone (I-PTH) ence of high circulating levels of non-1-84 PTH fragments should be three to five times normal to prevent adynamic bone (most likely 7-84 PTH) detected by the "intact" assay and the disease. In circulation, there is a non-(1-84) PTH-truncated antagonistic effects of 7-84 PTH on the biological activity of fragment, likely 7-84, which, in addition to PTH 1-84, is mea-1-84 PTH explain the need of higher levels of "intact" PTH sured by most I-PTH immunoradiometric (IRMA) assays, givto prevent adynamic bone disease. ing erroneously high I-PTH values. We have developed a new IRMA assay in which the labeled antibody recognizes only the first six amino acids of the PTH molecule. Thus, this new IRMA assay (Whole PTH) measures only the biologically active 1-84 Parathyroid hormone (PTH), a single-chain polypep-PTH molecule. tide of 84 amino acids [1], plays a critical role in the Methods. Using this new IRMA assay (Whole PTH) and the Nichols "intact" PTH assay, we compared the ability of regulation of mineral metabolism. Ionized calcium, caleach assay to recognize human PTH (hPTH) 1-84 and hPTH citriol, and phosphorus are the three major regulators 7-84 and examined the percentage of non-1-84 PTH in circulaof PTH homeostasis in humans. tion and in parathyroid glands. Possible antagonistic effects of The human PTH gene is located on the short arm of the 7-84 PTH fragment on the biological activity of 1-84 PTH chromosome 11. The coding region spans more than 4 in rats were also tested. Results. In 28 uremic patients, PTH values measured with kb and consists of three exons. The first exon contains the Nichols assay, representing a combined measurement of the 5Ј untranslated region of the PTH transcript. Theboth hPTH 1-84 and hPTH 7-84, were 34% higher than with coding sequence spans exons 2 and 3. The spliced cytothe Whole assay (hPTH 1-84 only); the median PTH was 523 plasmic transcript is 772 bases long. The primary translaversus 318 pg/mL (P Ͻ 0.001). Similar results were found in tion product, pre-pro-PTH (115 amino acids), is formed 14 renal transplant patients. In osteoblast-like cells, ROS 17.2, 1-84 PTH (10 Ϫ8 mol/L) increased cAMP from 18.1 Ϯ 1.25 to in the rough endoplasmic reticulum of parathyroid chief 738 Ϯ 4.13 mmol/well. Conversely, the same concentration of cells [2] and is converted within seconds to pro-PTH (90 7-84 PTH had no effect. In parathyroidectomized rats fed a amino acids) [3]. In the Golgi apparatus, pro-PTH is calcium-deficient diet, 7-84 PTH was not only biologically inacconverted to intact PTH (I-PTH; 84 amino acids) approxtive, but had antagonistic effects on 1-84 PTH in bone. Plasma calcium was increased (0.65 mg/dL) two hours after 1-84 PTH imately 15 minutes after the biosynthesis of the original tre...