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Gene Review

PTH  -  parathyroid hormone

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Disease relevance of PTH

  • Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease [1].
  • Because neonatal bovine and pathological human parathyroid glands show cellular hyperplasia, we studied the temporal relationship between cellular proliferation and the regulation of PTH release and cytosolic calcium concentration in cultured bovine parathyroid cells [2].
  • The PTH-related protein may have a role in the syndrome of humoral hypercalcemia of malignancy [3].
  • These findings suggest that stage-dependent increases in PTH/PTH-related peptide receptor levels localize the hormone stimulation of proteoglycan synthesis and inhibition of precocious hypertrophy in the matrix-forming zone of growth plates [4].
  • Pertussis toxin also increased PTH mRNA at a low extracellular Ca2+ concentration (0.7 mM) (4-fold increase) and a normal concentration (1.25 mM) (2-fold increase) [5].

High impact information on PTH


Chemical compound and disease context of PTH

  • Incubation with pertussis toxin (5 x 10(-9) M), which blocks the high-calcium-mediated inhibition of cyclic adenosine monophosphate accumulation in these cells, also reversed the inhibition of PTH mRNA levels at high Ca2+ (2.0 mM) with a marked increase in PTH mRNA levels [5].
  • In this study, we evaluated the effects of 17 beta-estradiol and progesterone on PTH secretion from abnormal parathyroid tissue from seven patients (four adenomas, three hyperplasia) [9].
  • Greater than 90% of tumor-bearing mice developed a syndrome of hypercalcemia, hypophosphatemia, hypercalciuria, elevated plasma 1,25-dihydroxyvitamin D, normal immunoreactive PTH, elevated urinary cAMP, and accelerated bone resorption compared to control mice [10].
  • Dispersed bovine parathyroid cells treated with or without 0.5 micrograms/ml pertussis toxin were tested with stimulatory (epinephrine, isoproterenol) or inhibitory (PGF2 alpha) agonists for responses in cAMP accumulation (5-min incubation) or PTH (90-min incubation) release [11].
  • Pertussis toxin produced an enhanced response to epinephrine (a mixed alpha-adrenergic and beta-adrenergic agonist) in cAMP production and in PTH secretion [11].

Biological context of PTH


Anatomical context of PTH

  • Sp3/Sp1 in the parathyroid gland: identification of an Sp1 deoxyribonucleic acid element in the parathyroid hormone promoter [13].
  • There was a close correlation between this progressive decrease in maximal inhibition of PTH release and the cytosolic calcium at high extracellular calcium in cultured cells (r = 0.99, P < 0.001) [2].
  • B-cell tolerance to human PTH was broken by immunisation with PTH peptides in adjuvant [15].
  • At later times of incubation (30-90 min), autoradiographic grains within the secretion glanules migrated to the periphery of the cell and to the plasma membrane, in correlation with the release of PTH first detected by 30 min [16].
  • We conclude that proteolytic conversion of Pre-ProPTH to ProPTH takes place in the RER and that subsequent conversion of ProPTH to PTH occurs in the Golgi complex [16].

Associations of PTH with chemical compounds

  • Inhibition of 1alphaOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D(3)-mediated suppression of PTH [1].
  • INTRODUCTION: In the rat, Ca(2+) and phosphate regulate PTH mRNA stability by the interaction of trans-acting proteins with a defined cis-acting instability element in the distal region of the PTH mRNA 3'-untranslated region (UTR) [12].
  • The existence of PTH-sensitive adenylate cyclase and the reproduction of increased epithelial Ca transport by dibutyryl-cAMP suggest that cAMP is the mediator [17].
  • Large amounts of PTH given to human subjects as serial injections or prolonged infusions cause decreased urinary 3',5'-cyclic adenosine monophosphate (cAMP) responses to subsequent PTH doses, but it is uncertain whether lower doses given over shorter periods similarly cause renal tachyphylaxis to PTH action [18].
  • Combined treatment with 10(-6) M retinoic acid and 10(-8) M 1,25(OH)2D3 more effectively decreased PTH secretion and preproPTH mRNA than did either compound alone [19].

Regulatory relationships of PTH


Other interactions of PTH

  • Study of the peptides produced from each form of PTH by cleavage with cyanogen bromide showed that peak II is oxidized at methionine 8 and peak III at methionine 18 while peak I is oxidized at both methionines [25].
  • 5. Inhibition of binding of tritiated hormone by unlabeled PTH was also highly effective at pH 6.0, but this apparently specific binding was also inhibited by adrenocorticotropic hormone, insulin, glucagon, and vasopressin [26].
  • PTHrP (1-34) and PTH (1-34) dose-dependently inhibited BVSMC calcification [27].
  • Incubation of DCT suspension with 10(-8) M bovine PTH (1-34) resulted in a significant increase in the Na(+)-dependent Ca++ uptake by the corresponding BLM vesicles [20].
  • Using preparations of dispersed bovine parathyroid cells, we have investigated the effect of a 16-residue synthetic peptide, ARF-16, which corresponds to the N-terminus of the ADP-ribosylation factor, on the secretion of PTH [28].

Analytical, diagnostic and therapeutic context of PTH


  1. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Ritter, C.S., Armbrecht, H.J., Slatopolsky, E., Brown, A.J. Kidney Int. (2006) [Pubmed]
  2. Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells. LeBoff, M.S., Shoback, D., Brown, E.M., Thatcher, J., Leombruno, R., Beaudoin, D., Henry, M., Wilson, R., Pallotta, J., Marynick, S. J. Clin. Invest. (1985) [Pubmed]
  3. Parathyroid hormone-related protein purified from a human lung cancer cell line. Moseley, J.M., Kubota, M., Diefenbach-Jagger, H., Wettenhall, R.E., Kemp, B.E., Suva, L.J., Rodda, C.P., Ebeling, P.R., Hudson, P.J., Zajac, J.D. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  4. Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation. Iwamoto, M., Jikko, A., Murakami, H., Shimazu, A., Nakashima, K., Iwamoto, M., Takigawa, M., Baba, H., Suzuki, F., Kato, Y. J. Biol. Chem. (1994) [Pubmed]
  5. Regulation of parathyroid hormone messenger RNA levels by protein kinase A and C in bovine parathyroid cells. Moallem, E., Silver, J., Naveh-Many, T. J. Bone Miner. Res. (1995) [Pubmed]
  6. Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent). Glover, D., Riley, L., Carmichael, K., Spar, B., Glick, J., Kligerman, M.M., Agus, Z.S., Slatopolsky, E., Attie, M., Goldfarb, S. N. Engl. J. Med. (1983) [Pubmed]
  7. Absence of parathyroid hormone messenger RNA in nonparathyroid tumors associated with hypercalcemia. Simpson, E.L., Mundy, G.R., D'Souza, S.M., Ibbotson, K.J., Bockman, R., Jacobs, J.W. N. Engl. J. Med. (1983) [Pubmed]
  8. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Brown, E.M., Gamba, G., Riccardi, D., Lombardi, M., Butters, R., Kifor, O., Sun, A., Hediger, M.A., Lytton, J., Hebert, S.C. Nature (1993) [Pubmed]
  9. Effects of estradiol and progesterone on parathyroid hormone secretion from human parathyroid tissue. Duarte, B., Hargis, G.K., Kukreja, S.C. J. Clin. Endocrinol. Metab. (1988) [Pubmed]
  10. Squamous carcinoma model of humoral hypercalcemia of malignancy. Gkonos, P.J., Hayes, T., Burtis, W., Jacoby, R., McGuire, J., Baron, R., Stewart, A.F. Endocrinology (1984) [Pubmed]
  11. Prostaglandin F2 alpha and alpha-adrenergic agonists regulate parathyroid cell function via the inhibitory guanine nucleotide regulatory protein. Fitzpatrick, L.A., Brandi, M.L., Aurbach, G.D. Endocrinology (1986) [Pubmed]
  12. Identification and characterization of cis-acting elements in the human and bovine PTH mRNA 3'-untranslated region. Bell, O., Silver, J., Naveh-Many, T. J. Bone Miner. Res. (2005) [Pubmed]
  13. Sp3/Sp1 in the parathyroid gland: identification of an Sp1 deoxyribonucleic acid element in the parathyroid hormone promoter. Alimov, A.P., Langub, M.C., Malluche, H.H., Koszewski, N.J. Endocrinology (2003) [Pubmed]
  14. Isolation and complete nucleotide sequence of the gene for bovine parathyroid hormone. Weaver, C.A., Gordon, D.F., Kissil, M.S., Mead, D.A., Kemper, B. Gene (1984) [Pubmed]
  15. Control of hypercalcaemia of parathyroid carcinoma by immunisation. Bradwell, A.R., Harvey, T.C. Lancet (1999) [Pubmed]
  16. Parathyroid hormone biosynthesis. Correlation of conversion of biosynthetic precursors with intracellular protein migration as determined by electron microscope autoradiography. Habener, J.F., Amherdt, M., Ravazzola, M., Orci, L. J. Cell Biol. (1979) [Pubmed]
  17. Effects of parathyroid hormone on cytosolic free calcium concentration in individual rabbit connecting tubules. Bourdeau, J.E., Lau, K. J. Clin. Invest. (1989) [Pubmed]
  18. Rapid development of renal resistance to low doses of synthetic bovine parathyroid hormone fragment 1-34. Dissociation of urinary cyclic adenosine monophosphate, phosphaturic, and calciuric responses. Law, W.M., Heath, H. J. Clin. Invest. (1983) [Pubmed]
  19. Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture. MacDonald, P.N., Ritter, C., Brown, A.J., Slatopolsky, E. J. Clin. Invest. (1994) [Pubmed]
  20. The mechanism of parathyroid hormone action on calcium reabsorption by the distal tubule. Bouhtiauy, I., Lajeunesse, D., Brunette, M.G. Endocrinology (1991) [Pubmed]
  21. The effect of parathyroid hormone and atrial natriuretic peptide on cyclic nucleotides production and proliferation of avian epiphyseal growth plate chondroprogenitor cells. Pines, M., Hurwitz, S. Endocrinology (1988) [Pubmed]
  22. Mode of action of somatostatin in inhibiting parathyroid hormone secretion. Kukreja, S.C., Hargis, G.K., Bowser, E.N., Williams, G.A. Horm. Metab. Res. (1980) [Pubmed]
  23. Parathyroid hormone-like peptide and parathyroid hormone are secreted from bovine parathyroid via different pathways. Connor, C., Drees, B., Hamilton, J. Biochim. Biophys. Acta (1993) [Pubmed]
  24. Parathyroid hormone-related protein inhibits indothelin-1 production. Jiang, B., Morimoto, S., Fukuo, K., Hirotani, A., Tamatani, M., Nakahashi, T., Nishibe, A., Niinobu, T., Hata, S., Chen, S., Ogihara, T. Hypertension (1996) [Pubmed]
  25. Oxidized forms of parathyroid hormone with biological activity. Separation and characterization of hormone forms oxidized at methionine 8 and methionine 18. Frelinger, A.L., Zull, J.E. J. Biol. Chem. (1984) [Pubmed]
  26. Binding of tritiated bovine parathyroid hormone to plasma membranes from bovine kidney cortex. Zull, J.E., Malbon, C.C., Chuang, J. J. Biol. Chem. (1977) [Pubmed]
  27. Parathyroid hormone-related peptide as a local regulator of vascular calcification. Its inhibitory action on in vitro calcification by bovine vascular smooth muscle cells. Jono, S., Nishizawa, Y., Shioi, A., Morii, H. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  28. Parathyroid hormone (PTH) secretion: stimulation of PTH secretion by a peptide derived from the adenosine diphosphate-ribosylation factor. Newman, L., Drees, B., Forte, L., Hamilton, J. Endocrinology (1994) [Pubmed]
  29. Introduction by molecular cloning of artifactual inverted sequences at the 5' terminus of the sense strand of bovine parathyroid hormone cDNA. Weaver, C.A., Gordon, D.F., Kemper, B. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  30. Nucleotide sequence of bovine parathyroid hormone messenger RNA. Weaver, C.A., Gordon, D.F., Kemper, B. Mol. Cell. Endocrinol. (1982) [Pubmed]
  31. Heterogeneous response to calcium by individual parathyroid cells. Sun, F., Ritchie, C.K., Hassager, C., Maercklein, P., Fitzpatrick, L.A. J. Clin. Invest. (1993) [Pubmed]
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