The Relationship between Vitamin D and Parathyroid Hormone.

Over three decades ago, it was established that deficiency of either vitamin D or parathyroid hormone may lead to tetany and hypocalcemia (1, 2). Since then, there has been continued interest in the relationship between the biologic effects of these two agents. At one time it was believed that the D vitamins exerted their effects by stimulating the parathyroid glands, but this concept became untenable after it was established that vitamin D could induce hypercalcemia in hypopara-thyroid organisms. More recently it has been proposed that the hormone exerts its characteristic effects only in vitamin D-fed animals (3), and that the basis of this action depends upon a chemical interaction between the two (4). These proposals are not satisfactory because there is considerable clinical and pathological evidence (5) suggesting that parathyroid hyperfunction exists in vitamin D deficiency. Certainly complete synergism of action seems most unlikely because of the well-established difference in the syndromes produced by their separate deficiencies (5). On the other hand, there is no satisfactory explanation for the persistent hypocalcemia in D-deficient animals, in spite of apparent parathyroid over-function, nor for the observations of Harrison, Harrison, and Park (3) that the administration of a standard dose of parathyroid hormone to a D-deficient rat results in little or no change in the concentration of either calcium or phosphate in the plasma. Another problem that has remained unresolved is the explanation of the phosphate retention that occurs in a D-deficient animal or human shortly after the initiation of specific therapy (6). Har-rison and Harrison (6) have favored the view that this retention is due to a direct action of vitamin D upon the renal tubular reabsorption of phosphate , whereas others (5) have considered it a consequence of decreased parathyroid gland activity. A possible new insight into the nature of the vitamin D and parathyroid hormone relationship has come from mitochondrial studies (7-11). It has been found that vitamin D and parathyroid hormone promote the release of calcium (as a phosphate salt or ion pair) from isolated mito-chondria (7), that they act synergistically, and that the presence of the vitamin is necessary for the hormone to exert this effect, although the converse is not true. The hormone has other effects upon the mitochondria that are neither produced by, nor dependent upon, the presence of vitamin D. These are the stimulation of phosphate (11), sulfate, and arsenate (9) accumulation, and a stimulation …