INTERACTION BETWEEN CALCIUM AND 1,25-DIHYDROXYVITAMIN-D(3) IN THE REGULATION OF PREPROPARATHYROID HORMONE AND VITAMIN-D RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN AVIAN PARATHYROIDS

Regulation of prepro-PTH and vitamin D receptor (VDR) mRNAs in the par athyroid glands was studied in chickens in vivo. The birds were raised to 21 days of age on a vitamin D-deficient diet with 1% calcium and 0 .65% phosphorous. At the end of this period, the chicks exhibited mark ed hypocalcemia and enlarged parathyroid glands. In three separate tri als, the birds were repleted for 6 days with vitamin D and different d ietary calcium and phosphate concentrations, with 2 mug/kg 1,25-dihydr oxyvitamin Da [1,25-(OH)2D3] and different dietary calcium concentrati ons (0.5%, 1.0%, or 1.8%), or with 2 or 10 mug/kg (1,25-OH)2D3 and 0.6 % or 1.9% calcium or were kept vitamin D3 deficient and fed 0.5%, 1.0% , or 1.8% dietary calcium. Vitamin D treatment when combined with a hi gh level of dietary calcium resulted in an increase in plasma calcium from 6 mg/dl to greater than 10 mg/dl, a decrease in PTH mRNA of 65%, and a 6- to 8-fold increase in VDR mRNA. In another experiment in whic h no vitamin D source was given and the diets contained increasing lev els of dietary calcium, plasma calcium increased significantly (5.5 vs . 7 mg/dl), while PTH mRNA decreased by 40% and VDR mRNA increased by 60%. Neither parathyroid gland weight nor total RNA was significantly affected. When chicks were repleted with 1,25-(OH)2D3, the increase in plasma calcium and VDR mRNA and the decrease in PTH mRNA were conside rably more pronounced than those in the absence of the vitamin D sourc e. Furthermore, in the presence of the hormone, parathyroid weight and total RNA decreased significantly with increasing concentrations of d ietary calcium. When the chicks were repleted, respectively, with the two levels of 1,25-(OH)2D3, a marked positive interaction was evident between the hormone and dietary calcium in affecting levels of PTH and VDR mRNA. These results suggest that both 1,25-(OH)2D3 and calcium pa rticipate in the regulation of PTH and VDR gene transcription in the a vian parathyroid gland. Whereas the action of 1,25-(OH)2D3 requires a minimal level of dietary calcium, calcium affects PTH and VDR gene tra nscription even in the absence of any vitamin D source.