Parathyroid hormone responses to catecholamines and to changes of extracellular calcium in cows.

Modifications of the plasma level of immunoreactive parathyroid hormone (PTH) in cattle were induced by changes of the plasma concentrations of epinephrine, isoproterenol, or calcium. During abrupt hypocalcemia, PTH, obtained by infusions with ethylene glycol-bis (beta-aminoethylether) N, N'-tetraacetate (EGTA), increased during the first 4-8 min. After a transient decline, the hormone levels rose again and remained elevated. Infusions of calcium suppressed the hypocalcemia-induced augmentation of PTH levels within a few minutes. Prolonged epinephrine (and isoproterenol) infusions also rapidly increased PTH levels, however, in this case, they returned to basal concentrations after 50-60 min. Additional epinephrine infusions could not further raise PTH values. Moreover, three short-lasting infusions of epinephrine (7 min each), given at 30-min intervals, increased PTH levels to the same extent, whereas additional infusions were much less effective. The PTH response to epinephrine was completely restored, when the interval after a prolonged epinephrine infusion had been prolonged to > 100 min. During moderate hypocalcemia, occurring at the end of EGTA infusions and lasting for 90 min, the PTH response to a short-lasting epinephrine infusion (7 min) was more pronounced than in normocalcemic animals. During severe hypocalcemia, in which superimposed short-lasting infusions of EGTA (7 min) led to an additional abrupt fall of plasma calcium concentrations but not to a corresponding additional rise of the PTH levels, epinephrine rapidly and further increased PTH concentrations. On the other hand, at the end of prolonged infusions of epinephrine, when additional infusions of epinephrine were ineffective in raising PTH levels, EGTA-induced hypocalcemia consistently increased PTH concentrations. The EGTA-induced augmentation of PTH levels was enhanced by epinephrine and isoproterenol but not by propranolol. The present findings indicate, that variations of the extracellular calcium concentrations and beta-adrenergic agonists modify PTH levels by two different and independent mechanisms. On the other hand, it appears that the magnitude of change of the PTH levels to either stimulus is partially modulated by exposure to the other.

Synthetic human calcitonin: analysis of antibodies obtained from various animal species and determination of immunoreactive hormone in human sera.

Antibodies to synthetic human calcitonin (hCT) were developed in rabbits, goats and mice. The free peptide (32 amino-acid residues, Mwt. 3418) was administered together with adjuvant, and the effect of various immunization procedures, as well as of different dose-levels, was evaluated comparatively. Synthetic hCT was found to be a good immunogen for the three animal species examined. The relative importance of various structural parts of the hCT molecule with regard to immunological specificity was determined by reference to the inhibition of the specific binding of 125I-hCT to antibodies by peptide fragments of hCT. All the antisera studied were directed to structural and/or conformational properties of the 11-28 or 11-32 amino acid sequence of hCT. Six different antisera from rabbits and goats were selected for radioimmunological assay of hCT on the basis of their inhibitory dose50-values and immunological specificity. To improve the sensitivity of the radioimmunoassay (RIA), we studied the preparation of radioiodinated hCT and assessed various parameters determining the sensitivity of the assay. Despite all the efforts, CT in human plasma from healthy subjects could not be determined with certainty. The difficulties encountered in the determination of normal levels of circulating CT are discussed in terms of the sensitivity of RIA and non-specific interference of serum factors with RIA.

Plasma kinetics of exogenous bovine parathyroid hormone in calves.

The metabolism of purified bovine parathyroid hormone-(1-84) [bPTH-(1-84)] administered i.v. by constant infusions or rapid injections was investigated in 11 normocalcemic calves. Plasma kinetics of bPTH-(1-84) were derived with a radioimmunoassay system which recognised the intact hormone but no fragments. The metabolic clearance rates ranged from 9.1-22.9 ml/min/kg. The disappearance of the intact hormone and the reversible appearance of its NH2- and COOH-terminal fragments was investigated with additional and specific radioimmunoassay systems. At 2 min after the i.v. injection of bPTH-(1-84) a NH2-terminal fragment (M approximately 3500) was recognised and at 4 and 20 min COOH-terminal fragments (M approximately 7000 and 3500, respectively) were detected. The survival time in the circulation of the intact hormone and of its fragments was comparable. In conclusion, bovine bPTH-(1-84) and its NH2- and COOH-terminal fragments are metabolised in normocalcemic calves within minutes.

Distribution of circulating immunoreactive components of parathyroid hormone in normal subjects and in patients with primary and secondary hyperparathyroidism: the role of the kidney and of the serum calcium concentration.

1. The distribution of intact parathyroid hormone-(1-84) [PTH-(1-84)] and of its COOH-terminal fragments was determined in human serum by column chromatography. In addition to PTH-(1-84) (peak I), COOH-terminal fragments having molecular weights of approximately 4000-7000 (peak II) and immunoreactive components co-eluting with human PTH-(1-12) (peak III) were observed. 2. Mean concentrations of intact PTH-(-84) and of its COOH-terminal fragments were significantly raised in chronic renal failure as compared with those of normal subjects. Mean amounts of peak II were higher in patients with chronic renal insufficiency than in nutritional vitamin D deficiency, in pseudohypoparathyroidism and in primary hyperparathyroidism, despite comparable amounts of PTH-(1-84). 3. In chronic renal failure as well as in a group of patients with vitamin D deficiency, pseudohypoparathyroidism and primary hyperparathyroidism and in controls, significant linear relations were found between the serum concentrations of calcium and log (peak II/peak I). Our findings suggest that the conversion of intact PTH-(1-84) into COOH-terminal fragments by the parathyroid glands (resulting in a raised secretion of fragments) and/or in peripheral organs may be directly related to the serum concentration of calcium. However, the degradation of the fragments may also be suppressed in a calcium-dependent manner.