Parathyroid hormone: Sequence, synthesis, immunoassay studies

Potts, John T.; Murray, Timothy M.; Peacock, Munro; Niall, Hugh D.; Tregear, G. W.; Keutmann, H. T.; Powell, David; Deftos, Leonard J.

doi:10.1016/0002-9343(71)90119-7

Cited by 129 publications

(36 citation statements)

References 14 publications

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“…Our findings suggest that while most nonparathyroid neoplasms causing hypercalcemia produce PTH-like peptides that react with the C-terminal-specific assay, not all have the concomitant production of biologically active PTH-like peptides and that osteolytic factors other than PTH may be causing the hypercalcemia in such patients as has been previously suggested (18). Previous studies (19,20) in patients with 1°HPT have shown that calcium infusions cause a suppression in both iPTH and UcAMP. Our data confirms this and also shows that patients with 1°HPT are equally as sensitive to changes in the serum calcium as are nornial subjects up to a calcium concentration of 10.5 mg/dl.…”

Section: Resultssupporting

confidence: 60%

Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.

Shaw¹,

Oldham²,

Rosoff³

et al. 1977

J. Clin. Invest.

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A B S T R A C T Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcitum infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, senrm calcium concentration, and carboxyl-terminal immtunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH.If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as ,umol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTHmediated hypercalcemia.

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Section: Resultssupporting

confidence: 60%

Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.

Shaw¹,

Oldham²,

Rosoff³

et al. 1977

J. Clin. Invest.

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“…Variable results have been reported concerning the quantity of parathyroid hormone found in plasma either in normal subjects or in patients with hyperparathyroidism. Furthermore, there are apparent disagreements with respect to control of hormone secretion in primary hyperparathyroidism (10,14,15). When one considers that the hormonal fragment or fragments present in blood may be detected by one antiserum but not by a second and, in addition, the fragment(s) may be cleared from the circulation at rates that are different than for the intact, recently-secreted hormone, then entirely different impressions would be gathered concerning not only absolute concentration of hormone, but also rates of hormone disappearance.…”

Section: Discussionmentioning

confidence: 99%

Parathyroid Hormone: Secretion and Metabolism In Vivo

Habener

Powell

Murray

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

128

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Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood (obtained by venous catheterization) from patients with hyperparathyroidism, as well as from calves and from cattle. Hormone secreted in vivo from normal bovine parathyroid glands and from human parathyroid adenomas is similar in size to the 84-amino-acid peptide (molecular weight of 9500) extracted from the parathyroids. However, much of the immunoreactive parathyroid hormone present in the peripheral circulation of man and cattle is smaller than the extracted or secreted hormone; it elutes from gel columns at a position corresponding to a molecular weight of about 7000. The immunological characteristics of extracted and secreted hormone are identical, while hormone in the general circulation is immunologically dissimilar to extracted and secreted hormone. The results indicate that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.Despite recent advances in the structural characterization of parathyroid hormone (extracted from parathyroids) (1)(2)(3) and the synthesis of a biologically active peptide consisting of the first 34 amino acids (5), recent findings based on radioimmunoassays have suggested that the biosynthesis and secretion, as well as the metabolism, of endogenous parathyroid hormone in man and animals is quite complex and that, in fact, the exact chemical nature of the active circulating form of the hormone is not yet known (3,(6)(7)(8)(9).Berson and Yalow reported that plasma parathyroid hormone is immunologically different from hormone extracted from tissue, but the chemical basis of this heterogeneity of plasma hormone could not then be determined (7). Other workers have subsequently reported finding immunological differences between the parathyroid hormone extracted from the glands and that found either in plasma or secreted into culture medium during incubation of parathyroid tissue (8, 9). In fact, Arnaud, et al. (6)

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“…Venous blood was collected in heparinized tubes from the antecubital vein from 24 patients in the fasting state. 19 had hyperparathyroidism and 5 were normal subjects (21). Samples from veins draining the parathyroid glands were collected at the time of diagnostic transfemoral catheterization in five patients with surgically proven parathyroid adenomas and in two patients without disorders of parathyroid function (cases 23 and 27 in reference 22).…”

Section: Methodsmentioning

confidence: 99%