Parathyroid Ablation in Dystrophic Hamsters

Abstract

A B S T R A C T Cumulative evidence indicates thatthere is an increased accumulation of calcium in dystrophic muscle and that this may have a pathophysiological role in the progression of the dystrophic process. The accumulation may be related to a defect of the plasma membrane. Because parathyroid hormone (PTH) stimulates calcium influx into the cytosol, the chronic effects of surgical ablation of the parathyroid glands on muscle Ca, Mg, protein synthesis, and histology, as well as plasma creatine phosphokinase (CPK), Ca, and Mg, were studied in normal and dystrophic (BIO 14.6) To determine the degree of dystrophy at the age when TPTX was performed, identical analyses were made in 35-d-old hamsters. Definitive histological signs of dystrophy were observed, and although the Ca content in heart, diaphragm, and rectus femoris was elevated, the values were lower than in 90-d-old intact and TPTX dystrophic hamsters. This indicates that chronic TPTX in dystrophic hamsters reduces, but does not arrest, the dystrophic process.In normal hamsters, a 50% reduction in plasma Ca concentration was observed 6 h after TPTX; 55 d after TPTX, however, plasma Ca was within normal limits in both normal and dystrophic hamsters. No parathyroid tissue was observed in serial sections of the trachea and adjacent tissues in TPTX animals. This suggests that in chronically TPTX hamsters fed a standard laboratory diet, plasma Ca can be maintained by mechanisms independent of parathyroid function.The data indicate that in dystrophic hamsters TPTX causes a marked reduction in: (a) muscle Ca accumulation, (b) levels of plasma CPK and, (c) intensity of histological changes in the heart. These changes were independent of the levels of plasma Ca and were not observed in normal hamsters. We conclude that PTH accentuates the dystrophic process, probably by enhancing the already increased Ca flux into muscle (apparently caused by defective sarcolemma). We postulate that normal secretion of PTH may have a deleterious effect in congenital or acquired conditions associated with altered plasma membranes.

Normocalcemia and persistent elevated serum concentrations of 1–84 parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of increased morbidity from cardiovascular disease

“…The possible individual contributions of increased 1-84 PTH and ionized calcium to cardiac abnormalities in patients with pHPT remain unresolved. Elevated 1-84 PTH and calcium both exert a hypertrophic effect on cardiomyocytes [14], whereas 1-84 PTH induces cellular calcium influx independent of serum calcium concentration [15,16]. Combining these observations with the present study and previous studies, it seems that elevated t-84 PTH concentration may contribute to postoperative cardiovascular disease in a subgroup of these patients.…”

Primary hyperparathyroidism and the heart: Cardiac abnormalities correlated to clinical and biochemical data

“…Thus our findings are in contrast to those of Katz et al [25], who are of the opinion that soft tissue calcification occurs only in patients with an elevated calcium-phosphate product. On the other hand Palmieri et al [39] concluded that PTH accentuates the dystrophic process by enhancing the already increased calcium flux into the heart muscle. They also postulated that normal secretion of PTH may have a deleterious effect in congenital or acquired conditions associated with altered plasma membranes [39].…”

Effect of Exogenous Arginine Vasopressin on Adrenocorticotropin and Cortisol Release in Myotonie Dystrophy Patients: Delayed Responses of Normal Magnitude

“…Other workers (14), using graded iv infusions of AVP in normal humans, showed that it was necessary to achieve peripheral festations of the same more general biochemical abnormality, such as an abnormality in structure or function in one or more proteins involved in calcium transport. Some evidence pointing towards defective calcium transport in M D includes increased calcium permeability in erythrocyte membranes from M D patients (17), and the ability of normal levels of parathyroid hormone in the presence of defective membranes in dystrophic hamster muscle cells, to abnormally enhance calcium influx (18). If M D corticotropes are similarly subject to enhanced calcium influx, this may cause the abnormal increase in the initial and sustained ACTH responses to C R H previously reported by us (2), as these depend on both extracellular Ca2' (CaZte) influx and sustained increases in intracellular C a z + (Ca2 t i ) concentration (16, 19).…”