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.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001846:Bone Development; D002118:Calcium / Q000378:metabolism; D002762:Cholecalciferol / Q000096:biosynthesis / Q000378:metabolism; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006887:Hydroxycholecalciferols; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010280:Parathyroid Glands / Q000502:physiology; D010758:Phosphorus / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000378:metabolism / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D014807:Vitamin D; D002762:Cholecalciferol; D010758:Phosphorus; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium