Recent advances in our understanding of the vitamin D endocrine system.

Vitamin D3 gives rise to at least one hormone in which the kidney is utilized as an endocrine system. This hormone arises from 25-OH-D3 which in turn is synthesized in the liver from vitamin D3. The production of this calcium and phosphorus mobilizing hormone, namely 1,25-(OH)2D3, is strongly regulated by the need for calcium and phosphorus. The regulation of its production can occur only after initial 1,25-(OH)2D3 is made and brings about the appearance of 25-OH-D3-24hydroxylase. The need for calcium brings about a stimulation of parathyroid hormone secretion. The parathyroid hormone suppresses the 24-hydroxylase and stimulates the 1-hydroxylase. Alternatively, the need for phosphorus directly stimulates the 1-hydroxylase and suppresses the 24-hydroxylase. The 24-hydroxylation appears to be the initial reaction leading to the inactivation and excretion of vitamin D whereas the 1-hydroxylation is the reaction bringing about the activation of the molecule to 1,25-(OH)2D3. The 1,25-(OH)2D3, the 25-OH-D3 and an analog of 1,25-(OH)2D3, namely 1alpha-OH-D3, are potentially extremely useful in the treatment of metabolic bone diseases such as renal osteodystrophy, hepatically related disorders of calcium and bone metabolism, hypoparathyroidism, and vitamin D dependency disease. The 1alpha-OH-D3 is effective by virtue of its conversion to 1,25-(OH)2D3. The 25-hydroxylation of both 1alpha-OH-D3 and vitamin D3 itself occurs predominantly in the liver. Finally, it is not entirely settled whether 1,25-(OH)2D3 is active directly in all of the functions of viramin D or whether it must be further converted metabolically. A new metabolic pathway for vitamin D has been discovered in which 1,25-(OH)2D3 loses its 26 and 27 carbons to carbon dioxide, producing an unknown metabolite. It is not certain whether this pathway represents degradation of the 1,25-(OH)2D3 or its further activation.