Hypercalcaemia of Neoplasia, Parathyroid Hormone and Vitamin D: Studies in Parabiosis

Abstract

A localized transplantable Leydig cell tumour of the Fischer rat regularly produces lethal hypercalcaemia in thyroparathyroidectomized and intact hosts. The parabiosis model was used to explore and compare the hypercalcaemia producing action of this tumour, parathyroid hormone, and vitamin D. Administration of exogenous parathyroid hormone (10 and 20 units) to one thyroparathyroidectomized parabiont rat increased the serum calcium in both parabionts within 24 hours. Endogenous parathyroid hormone, studied by producing parabiosis between thyroparathyroidectomized rats and intact rats, raised the serum calcium of the thyroparathyroidectomized parabiont within 7 days in parabiosis, suggesting that endogenous parathyroid hormone is effective across the parabiotic union. Vitamin D3 (100 000 and 150 000 units) given to one parabiont of a thyroparathyroidectomized pair produced hypercalcaemia only in the injected parabionts. When the hypercalcaemia producing tumour was grown in thyroparathyroidectomized pairs for 3\p=n-\6 weeks, severe hypercalcaemia and death occurred only in the tumour bearing parabiont. The serum calcium of the non-tumour parabiont did rise over a period of 3\p=n-\6weeks and was compatible with an approach to calcium

The hypercalcemic rat leydig cell tumor—A model of the humoral hypercalcemia of malignancy

“…The hypercalcemia in this model is associated with hypophosphatemia and renal phosphate wasting, as has been shown before [9][10][11]. In this study, we have found that the hypercalcemia is also associated with increased urinary cAMP excretion and low immunoreactive iPTH concentrations, also recently associated with the humoral Hypercalcemia of malignancy [7,19].…”

“…The tumors grown rapidly to a very large size but do not metastasize. Previous workers have shown that the hypercalcemia caused by these tumors is associated with hypercalciuria, phosphaturia, and hypophosphatemia [9][10][11]. In this study, we have further characterized this model and shown that it has the other features of the humoral hypercalcemia associated with human malignancies, including increased urinary cAMP excretion, renal phosphate wasting, and suppressed circulating iPTH concentrations.…”

“…A number of studies on the mechanism of hypercalcemia in the rat Leydig cell tumor have been performed in the past [9][10][11]. These earlier studies showed that hypercalcemia was associated with hypercalciuria and hypophosphatemia.…”

Biochemical Monitoring of Cancer: A Review

“…However, in women, other osteolytic factors, possibly peptides, are also released in-vitro by human breast tumours. This factor may be related to the hypercalcaemic agent formed by an experimental rat Leydig cell tumour (ponthier and Rice, 1974).…”

Geriatric Malignancies and Their Hormonal Aspects

“…From exten sive studies, it can be said only that the hormone produced is probably not parathyroid hormone nor vitamin D or one of its metabolites [26], It is probably of small molecular weight and rapidly metabolized. …”