Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1986 November; 78(5): 1296–1301.
PMCID: PMC423816

Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat.


In vitro 1,25-dihydroxycholecalciferol (1,25(OH)2D3) decreased levels of preproparathyroid(preproPTH) hormone mRNA. We have now pursued these studies in vivo in the rat. Rats were administered vitamin D metabolites i.p. and the levels of preproPTH mRNA were determined in excised parathyroid-thyroid glands by blot hybridization. PreproPTH mRNA levels were less than 4% of basal at 48 h after 100 pmol 1,25(OH)2D3, with no increase in serum calcium. Gel blots showed that 1,25(OH)2D3 decreased preproPTH mRNA levels without any change in its size (833 basepair). Microdissected parathyroids after 1,25(OH)2D3 (100 pmol) showed mRNA levels for preproPTH were 40 +/- 8% of controls, but for beta-actin were 100% of controls. The relative potencies of vitamin D metabolites were: 1,25(OH)2D3 greater than 24,25(OH)2D3 greater than 25(OH)D3 greater than vitamin D3. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' PTH transcription was 10% of control, while beta-actin was 100%. These results show that 1,25(OH)2D3 regulates PTH gene transcription. PTH stimulates 1,25(OH)2D3 synthesis, which then inhibits PTH synthesis, thus completing an endocrinological feedback loop.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Habener JF, Rosenblatt M, Potts JT., Jr Parathyroid hormone: biochemical aspects of biosynthesis, secretion, action, and metabolism. Physiol Rev. 1984 Jul;64(3):985–1053. [PubMed]
  • Fraser DR. Regulation of the metabolism of vitamin D. Physiol Rev. 1980 Apr;60(2):551–613. [PubMed]
  • Hughes MR, Haussler MR. 1,25-Dihydroxyvitamin D3 receptors in parathyroid glands. Preliminary characterization of cytoplasmic and nuclear binding components. J Biol Chem. 1978 Feb 25;253(4):1065–1073. [PubMed]
  • Wecksler WR, Ross FP, Mason RS, Posen S, Norman AW. Biochemical properties of the 1 alpha, 25-dihydroxyvitamin D3 cytoplasmic receptors from human and chick parathyroid glands. Arch Biochem Biophys. 1980 Apr 15;201(1):95–103. [PubMed]
  • Tsai HC, Norman AW. Studies on calciferol metabolism. 8. Evidence for a cytoplasmic receptor for 1,25-dihydroxy-vitamin D3 in the intestinal mucosa. J Biol Chem. 1973 Sep 10;248(17):5967–5975. [PubMed]
  • Chen TL, Hirst MA, Feldman D. A receptor-like binding macromolecule for 1 alpha, 25-dihydroxycholecalciferol in cultured mouse bone cells. J Biol Chem. 1979 Aug 25;254(16):7491–7494. [PubMed]
  • Wecksler WR, Henry HL, Norman AW. Studies on the mode of action of calciferol. Subcellular localization of 1,25-dihydroxyvitamin D3 in chicken parathyroid glands. Arch Biochem Biophys. 1977 Sep;183(1):168–175. [PubMed]
  • Stumpf WE, Sar M, Reid FA, Tanaka Y, DeLuca HF. Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science. 1979 Dec 7;206(4423):1188–1190. [PubMed]
  • Silver J, Russell J, Sherwood LM. Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4270–4273. [PubMed]
  • Cantley LK, Russell J, Lettieri D, Sherwood LM. 1,25-Dihydroxyvitamin D3 suppresses parathyroid hormone secretion from bovine parathyroid cells in tissue culture. Endocrinology. 1985 Nov;117(5):2114–2119. [PubMed]
  • Scherzer P, Wald H, Czaczkes JW. Na-K-ATPase in isolated rabbit tubules after unilateral nephrectomy and Na+ loading. Am J Physiol. 1985 Apr;248(4 Pt 2):F565–F573. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Lehrach H, Diamond D, Wozney JM, Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. [PubMed]
  • Rigby PW, Dieckmann M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. [PubMed]
  • Schibler U, Hagenbüchle O, Wellauer PK, Pittet AC. Two promoters of different strengths control the transcription of the mouse alpha-amylase gene Amy-1a in the parotid gland and the liver. Cell. 1983 Jun;33(2):501–508. [PubMed]
  • Groudine M, Peretz M, Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. [PMC free article] [PubMed]
  • O'Malley BW. Steroid hormone action in eucaryotic cells. J Clin Invest. 1984 Aug;74(2):307–312. [PMC free article] [PubMed]
  • Wark JD, Tashjian AH., Jr Regulation of prolactin mRNA by 1,25-dihydroxyvitamin D3 in GH4C1 cells. J Biol Chem. 1983 Oct 25;258(20):12118–12121. [PubMed]
  • Heinrich G, Kronenberg HM, Potts JT, Jr, Habener JF. Parathyroid hormone messenger ribonucleic acid: effects of calcium on cellular regulation in vitro. Endocrinology. 1983 Feb;112(2):449–458. [PubMed]
  • Russell J, Lettieri D, Sherwood LM. Direct regulation by calcium of cytoplasmic messenger ribonucleic acid coding for pre-proparathyroid hormone in isolated bovine parathyroid cells. J Clin Invest. 1983 Nov;72(5):1851–1855. [PMC free article] [PubMed]
  • Rasmussen H, Matsumoto T, Fontaine O, Goodman DB. Role of changes in membrane lipid structure in the action of 1,25-dihydroxyvitamin D3. Fed Proc. 1982 Jan;41(1):72–77. [PubMed]
  • Golden P, Greenwalt A, Martin K, Bellorin-Font E, Mazey R, Klahr S, Slatopolsky E. Lack of a direct effect of 1,25-dihydroxycholecalciferol on parathyroid hormone secretion by normal bovine parathyroid glands. Endocrinology. 1980 Aug;107(2):602–607. [PubMed]
  • Au WY. Inhibition by 1,25 dihydroxycholecalciferol of hormonal secretion of rat parathyroid gland in organ culture. Calcif Tissue Int. 1984 Jul;36(4):384–391. [PubMed]
  • Chertow BS, Baylink DJ, Wergedal JE, Su MH, Norman AW. Decrease in serum immunoreactive parathyroid hormone in rats and in parathyroid hormone secretion in vitro by 1,25-dihydroxycholecalciferol. J Clin Invest. 1975 Sep;56(3):668–678. [PMC free article] [PubMed]
  • Brown EM. Four-parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue. J Clin Endocrinol Metab. 1983 Mar;56(3):572–581. [PubMed]
  • Slatopolsky E, Weerts C, Thielan J, Horst R, Harter H, Martin KJ. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients. J Clin Invest. 1984 Dec;74(6):2136–2143. [PMC free article] [PubMed]
  • Madsen S, Olgaard K, Ladefoged J. Suppressive effect of 1,25-dihydroxyvitamin D3 on circulating parathyroid hormone in acute renal failure. J Clin Endocrinol Metab. 1981 Oct;53(4):823–827. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation