Summary
The conversion of 25-hydroxyvitamin D3 (25 OH D3 ) to 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ), 24,25-dihydroxyvitamin D3 (24,25-(OH)2 D3 ) and 1,24,25-trihydroxyvitamin D3 (1,24,25-(OH)3 D3 ) was studied in renal tubules prepared from chicks raised on a vitamin D deficient
diet with or without vitamin D supplementation. As described previously, in tubules
from vitamin D deficient chicks, cyclic AMP caused an increase in the net accumulation
of 1,25-(OH)2 D3 , the major metabolite formed under these circumstances. This stimulation was shown
to be due to an increased maximum velocity of the hydroxylation reaction. There was
also a significant inhibition of the net accumulation of 24,25-(OH)2 D3 . Cyclic GMP caused a significant inhibition of 1,25-(OH)2 D3 formation and stimulation of the net accumulation of 24,25-(OH)2 D3 . In chicks supplemented with high doses of vitamin D, 24,25-(OH)2 D3 was the major metabolite of 25 OH D3 detected and 1-hydroxylase activity was negligible. Under these circumstances, neither
cyclic AMP nor cyclic GMP affected net accumulation of 24,25-(OH)2 D3 . This suggested that the apparent effect of the nucleotides on formation of 24,25-(OH)2 D3 may have been due to further metabolism of 24,25-(OH)2 D3 when 1-hydroxylase activity was high.
It is concluded that cyclic AMP and cyclic GMP have reciprocal effects on renal 25
OH D3 -1-hydroxylase activity, and both should be considered potential intracellular regulators
of 25 OH D3 metabolism.
Key-Words:
1,25-Dihydroxyvitamin D
3
-
Cyclic AMP
-
Cyclic GMP
