Interaction between calcium and 1,25-dihydroxyvitamin D3 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 parathyroid 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 marked hypocalcemia and enlarged parathyroid glands. In three separate trials, the birds were repleted for 6 days with vitamin D and different dietary calcium and phosphate concentrations, with 2 micrograms/kg 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and different dietary calcium concentrations (0.5%, 1.0%, or 1.8%), or with 2 or 10 micrograms/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 high 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 which no vitamin D source was given and the diets contained increasing levels 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 considerably more pronounced than those in the absence of the vitamin D source. Furthermore, in the presence of the hormone, parathyroid weight and total RNA decreased significantly with increasing concentrations of dietary 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 participate in the regulation of PTH and VDR gene transcription in the avian parathyroid gland. Whereas the action of 1,25-(OH)2D3 requires a minimal level of dietary calcium, calcium affects PTH and VDR gene transcription even in the absence of any vitamin D source.
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
J
J
Russell
A
A
Bar
L M
LM
Sherwood
S
S
Hurwitz
D000818:Animals; D002117:Calcitriol / Q000502:physiology*; D002118:Calcium / Q000097:blood / Q000502:physiology*; D002136:Calcium, Dietary / Q000494:pharmacology; D002645:Chickens / Q000378:metabolism; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000235:genetics; D014808:Vitamin D Deficiency / Q000097:blood
D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D011498:Protein Precursors; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C019056:preproparathormone; D002117:Calcitriol; D002118:Calcium