Influence of Vitamin D on Parathyroid Hormone-Induced Adenosine 3′,5′-Monophosphate Production by Bone Cells Isolated from Rat Calvariae*

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Abstract
This study was designed to explore a possible basis for the long-standing observation that optimal effects of parathyroid hormone (PTH) on mobilization of skeletal Ca require the presence of vitamin D. Calvariae were taken from 3- week-old rat pups born and suckled by mothers either deprived of dietary vitamin D (−D) or fed 5 IU vitamin Da/g diet from the sixth day of pregnancy (+D). Some −D pups also were injected with 50 ng 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 48 and 24 h before sacrifice. Bone cell populations responsive to PTH were isolated freshly by sequential enzymic digestion and centrifugation; then they were exposed to PTH in vitro, and cAMP production was measured. In some experiments, cells were preincubated 18 h with 1,25-(OH)2D3 (2 ng/ml) before exposure to PTH. Basal levels of cAMP were reduced in bone cells from hypocalcemic −D rats, and these cells also showed approximately a 50% reduction in the cAMP response to PTH compared to that of bone cells from +D pups. In bone cells from pups injected with 1,25-(OH)2D3, blood Ca was increased, and the in vitro bone cell cAMP response was increased to a level intermediate between that of -D and +D cells, indicating a partial restoration of the impaired cAMP response found with -D bone cells. Exposure of bone cells from +D rats, but not -D rats, to 1,25-(OH)2D3 in vitro led to a reduction in the subsequent cAMP response to PTH. We propose that the reduced cAMP response to in vitro 1,25-(OH)2D3 represents the heterologous desensitization described by others, while the reduced response to in vivo D deprivation involves homologous desensitization resulting from persistent hypocalcemia and chronic elevation of circulating PTH. This latter finding may help explain the reduced skeletal response to PTH during vitamin D deficiency.