The formation of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol by chick kidney homogenates is inhibited by increasing concentrations of Ca(2+). The apparent K(m) for the hydroxylation reaction is 1x10(-7)m, significantly lower than that reported for isolated mitochondria. Separated cytoplasmic and particulate fractions are inactive, but on recombination activity is restored, possibly because of the presence in the soluble fraction of a factor with a high affinity for 25-hydroxycholecalciferol.

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The chemistry and physiology of calcitonin are reviewed with particular emphasis on the evolution of the hormone and its modern role in humans. It seems likely that the relative deficiency of calcitonin in women may be important in postmenopausal bone loss. A major therapeutic application of calcitonin is in the treatment of Paget's disease of bone, and current recommendations for therapy are presented.

Many factors influence the production of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol) by the kidney. One important factor seems to be feedback regulation by 1,25(OH)2D3 itself. Administration of 1,25(OH)2D3 to vitamin D-deficient chicks abolishes renal 25(OH)D3(25-hydroxycholecalciferol)1-hydroxylase activity and induces the appearance of 25(OH)D3 24-hydroxylase activity. It is likely that these effects are mediated via a nuclear effect, as they are prevented by pretreatment with actinomycin D and alpha-amanitin. Further, 1,25(OH)2D3 has a marked effect on gene transcription in the kidney cell, as assessed by measurement of RNA polymerase activities. RNA polymerase I and II activities are 80-90% inhibited by 12.5nmol of 1,25(OH)2D3 within 30min of subcutaneous administration, indicating an immediate and massive decrease in total gene transcription. By 4h RNA polymerase II activity has returned to control values, but RNA polymerase I activity is markedly enhanced. These results are consistent with the view that regulation of cholecalciferol metabolism in the kidney is associated with an effect of the active metabolite on the kidney nucleus.