title: Rat calcium-sensing receptor is regulated by vitamin D but not by calcium.
abstract: Parathyroid hormone (PTH) secretion is regulated by extracellular calcium acting through a cell surface calcium receptor (CaR). We have examined the potential regulation of the CaR in the parathyroid glands (PTG) and kidney by calcium and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Rats fed vitamin D-deficient (-D) diets containing 0.02, 0.4, or 2.0% Ca had a wide range of serum ionized Ca (2.5-5.2 mg/dl) and PTH (22-590 pg/ml) concentrations. PTG CaR mRNA did not vary significantly with ionized calcium or PTH, indicating that hypocalcemia and hyperparathyroidism may not alter CaR expression. However, PTG CaR mRNA was 40% lower in the -D rats than in age-matched rats fed a vitamin D-replete (+D) diet (P < 0.002). Repletion of -D rats with 1,25-(OH)2D3 produced a dose-dependent increase in PTG CaR mRNA. Treatment of +D rats with 100 ng of 1,25-(OH)2D3 increased CaR mRNA by 33% (P < 0.05) and 54% (P < 0.002) in the PTG and by 89% (P < 0.02) and 91% (P < 0.02) in the kidney in two independent experiments. PTG CaR peaked at 16 h (150% of control, P < 0.05) after 1,25-(OH)2D3 administration but returned to normal by 24 h. This upregulation of CaR expression by 1,25-(OH)2D3 may be involved in the suppressive effects of vitamin D compounds on PTH secretion.
authors.affiliation: Department of Medicine, Washington University, St.Louis, Missouri 63110, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Zhong
authors.forename: J
authors.initials: J
authors.lastname: Finch
authors.forename: C
authors.initials: C
authors.lastname: Ritter
authors.forename: R
authors.initials: R
authors.lastname: McCracken
authors.forename: J
authors.initials: J
authors.lastname: Morrissey
authors.forename: E
authors.initials: E
authors.lastname: Slatopolsky
mesh_terms: D000818:Animals; D001483:Base Sequence; D002136:Calcium, Dietary / Q000008:administration & dosage*; D004032:Diet; D008969:Molecular Sequence Data; D010280:Parathyroid Glands / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014807:Vitamin D / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D002136:Calcium, Dietary; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat; D014807:Vitamin D