Parathyroid hormone and vitamin D

Abstract

PARATHYROID hormone (PTH) and vitamin D are the two most important regulators of calcium metabolism. In addition, both of these substances have marked effects upon citrate metabolism. The evidence for a link between citrate and calcium metabolism may be summarized as follows : (1) Administration of either vitamin D or PTH results in an increase in the amount of citrate and calcium in serum. Conversely, a deficiency of vitamin D, or a lack of FTH, results in a fall in serum citrate and calcium [l-15]. (2) An increase in the level of circulating citrate, whether produced by (a) injections of citrate as such [16]; (b) by the administration of fluoroacetate [17]; or (c) by nephrectomy [I, 17, 181, all result in hypercalcemia or bone resorption [19, 201. This review concerns the relationships between FTH, vitamin D, citrate, and calcium metabolism. The points to be considered are these: (1) the source of the citrate found in the serum after vitamin D or PTH administration; (2) the effect of vitamin D and PTH upon citrate metabolism in the bone, kidney and intestine; (3) the role of citrate in FIX-mediated calcium homeostasis; and (4) the interaction between vitamin D and PTH. General aspects of the biochemistry of parathyroid hormone have been discussed in a previous review [13]. Noteworthy among the existing studies are those of DE LUCA and associates [21, 221. These investigators demonstrated that vitamin D inhibits the oxidation of citrate by the kidney. This could account for the rise in the serum citrate level observed by many investigators after vitamin D administration. A similar rise in the serum citrate level is observed if citrate oxidation by the kidneys is prevented by removing them entirely [ 1, 17, 181. The kidneys have been shown to be the chief organs responsible for the removal of citrate from the blood [18, 231. The possibility of a direct effect of vitamin D on citrate metabolism in the bone must also be considered. CARLSSON and HOLLUNGER [3] have postulated that vitamin D stimulates citric acid production by bone. The administration of vitamin D to rats deficient in the vitamin has been found to increase markedly the plasma citric acid response to nephrectomy [24]. This observation suggests the existence of an extrarenal site of action of vitamin D on citrate metabolism. The most likely possibility is the bone, but there is no direct evidence supporting this view. NEUMAN