Arnaud, Claude D.

The later stages of the vitamin D deficiency syndrome during infancy are associated with impaired renal tubular reabsorption of amino acids, phosphate, and other metabolites. Secondary hyperparathyroidism has been implicated as the cause of the renal abnormality. Serum immunoreactive parathyroid hormone levels are elevated in infants with vitamin D deficiency (60 to 238 µl Eq/ml; normal < 40 µl q/ml). The highest levels were found in the more advanced stages of vitamin D deficiency.

Abstract Although levels of serum immunoreactive parathyroid hormone (iPTH) increase with age in women, this could be caused by retention of non-biologically active PTH fragments by the aging kidney. In 102 normal women, aged 30 to 89 yr, serum iPTH increased with age by 58% (r = 0.33, p < 0.001) with antiserum GP-1M (which has midmolecule specificity) and 43% (r = 0.32, p < 0.001) with antiserum CH-12M (which may have whole molecule specificity); urinary cAMP/GFR excretion increased by 29% (r = 0.22, p < 0.05). The results of these assays were validated by comparison with serum levels of biologically active PTH (BioPTH) in immunoextracts of serum followed by renal adenylate cyclase assay in a selected subgroup of 25 of the women. Serum BioPTH correlated with serum iPTH assessed by antiserum GP-1M (r = 0.48, p < 0.05) and antiserum CH-12M (r = 0.48, p < 0.05) but not with urinary cAMP. The data are consistent with an increase of parathyroid function with aging: clearly, we do not find decreased parathyroid function as would be expected if age-related bone loss was not mediated, in part, by PTH.

Hormones and purine nucleosides and nucleotides induced cultured bone cells to transform transiently from a spherical to a stellate shape. Cytochalasin B also induced the transformation. The change was blocked by colchicine and vinblastine, but not by lumicolchicine or cycloheximide. This morphologic transformation may provide a dynamic model of hormone action and bone cell modulation in vitro.

Serum immunoreactive parathyroid hormone (IPTH) is normal in patients with X-linked hypophosphatemic rickets who are not treated with phosphate salts. Phosphate raises IPTH in these patients. Endogenous IPTH does not influence the existing defect in tubular reabsorption of phosphate in male patients.

Biologically active 125 I-labeled bovine parathyroid hormone (prepared by electrolytic iodination) and its synthetic NH 2 -terminal (1-34) biologically active fragment bound rapidly and specifically to a purified plasma membrane preparation from bovine renal cortex. Binding of labeled intact hormone or labeled NH 2 -terminal (1-34) peptide was inhibited competitively by unlabeled (1-34) peptide in the same range of concentrations that activated renal cortical 3′:5′-adenylate cyclase (EC 4.6.1.1) in these membranes. The concentrations of synthetic (1-34) peptide for half-maximal inhibition of binding of labeled hormone as well as half-maximal activation of the enzyme were about 0.6 μM (2.5 μg/ml). Therefore it is likely that the binding activity studied represents a physiologically important renal receptor for parathyroid hormone. Biologically inactive (oxidized) forms of parathyroid hormone and (1-34) NH 2 -terminal peptide as well as calcitonin, glucagon, insulin, and epinephrine failed to competitively inhibit the binding of labeled (1-34) parathyroid hormone or activate adenylate cyclase in the renal cortical membrane preparation. Observations with the NH 2 -terminal (1-34) biologically active fragment of parathyroid hormone suggest that the COOH-terminal region of the molecule is not required for receptor binding.

An enzymatic activity that catalyzes the conversion of glandular parathyroid hormone to a smaller-molecular-weight, biologically and immunologically active form of this hormone has been extracted from normal parathyroid and other porcine tissues. The product of the conversion has the immunologic characteristics of the hormone that occurs in peripheral serum and in tissue culture medium from parathyroid explants. The enzyme is activated by chelating agents and is inhibited by high calcium concentrations, suggesting that this enzyme may be important in the regulation of secretion or metabolism of the hormone.

We have produced an antiserum to porcine parathyroid hormone (PTH) which distinguishes between the PTH in human hyperparathyroid serum and that in extracts of parathyroid adenomata. The PTH secreted into the medium by parathyroid adenoma slices in culture reacts with this antiserum in the same way as the PTH in human hyperparathyroid serum, but extraction of the same serum by a conventional procedure used for the extraction of glandular tissue converts the serum hormone to a species which reacts more like hormone extracted from adenomata. The results suggest that we have immunologically identified a native molecular species of PTH, that the antiserum used recognizes primarily this species in human hyperparathyroid serum, and that the PTH extracted from parathyroid adenomata is immuno-chemically altered.