Parathyroid hormone-like changes in renal calcium and phosphate reabsorption induced by Leydig cell tumor in thyroparathyroidectomized rats.
The Leydig cell tumor Rice H-500 is a model of humoral hypercalcemia of malignancy. Hypercalcemia is considered to result mainly from increased bone resorption. However, a change in renal tubular reabsorption of calcium (Ca) as a contributing factor to the hypercalcemia has not yet been recognized. The purpose of this study was to examine whether the renal handling of Ca was altered in Leydig cell tumor-bearing rats. To avoid counterregulations by Ca-regulating hormones, the effect of the Leydig cell tumor on plasma Ca and phosphate (Pi), urinary Ca and Pi excretion, as well as Ca and Pi renal tubular reabsorptive capacity was investigated in thyroparathyroidectomized rats. Clearance experiments were conducted at a time of tumor development when the glomerular filtration rate was not compromised. Under these conditions, tubular reabsorption of Ca was stimulated, and the maximal tubular reabsorption of Pi was markedly reduced (2.69 +/- 0.27 vs. 4.57 +/- 0.21 mumol/min; P less than 0.001). These changes were accompanied by increased urinary cAMP excretion (77.1 +/- 6.3 vs. 34.7 +/- 2.8 pmol/ml glomerular filtrate; P less than 0.001). These results indicate that the Leydig cell tumor produces a factor with PTH-like activity on the renal tubular reabsorption of Ca and Pi. The increased tubular reabsorption of Ca may play an important role in the pathogenesis of Leydig cell tumor-induced hypercalcemia. This animal model appears to be particularly appropriate for studying the mechanisms of certain types of humoral hypercalcemia of malignancy, as some cancer patients display a change in the renal handling of Ca similar to that observed in primary hyperparathyroidism.
D000042:Absorption; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007984:Leydig Cell Tumor / Q000378:metabolism*; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D010710:Phosphates; D002117:Calcitriol; D002118:Calcium