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Gene Review

PTH2  -  parathyroid hormone 2

Homo sapiens

Synonyms: Parathyroid hormone 2, TIP39, TIPF39, Tuberoinfundibular peptide of 39 residues
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High impact information on TIP39

  • Tuberoinfundibular peptide of 39 residues (TIP39) was recently purified from bovine hypothalamus based on selective PTH2 receptor activation [1].
  • The C-terminal helix of TIP39 differs from that of PTH with respect to size and amphipathicity, suggesting an altered mode of binding for TIP39, consistent with the receptor chimera and ligand truncation studies presented in the accompanying paper (Hoare, S. R. J., Clark, J. A., and Usdin, T. B. (2000) J. Biol. Chem. 275, 27274-27283) [2].
  • The recently identified natural peptide ligand, tuberoinfundibular peptide of 39 residues (TIP39) for the parathyroid hormone-2 (PTH2) receptor has been structurally characterized by high resolution NMR, circular dichroism, and computer simulations [2].
  • The structural characterization of TIP39 also provides some insight into the lack of affinity of this novel ligand for the PTH1 receptor [2].
  • The human PTH receptor type 2 (PTH2R) is activated by PTH and tuberoinfundibular peptide of 39 residues (TIP39), resulting in cAMP and intracellular Ca signaling [3].

Biological context of TIP39


Anatomical context of TIP39

  • TIP39 peptide levels in cell bodies change in parallel with mRNA levels, whereas TIP39 appears and disappears somewhat later in nerve fibers [7].
  • However, several hypothalamic nuclei projecting to the median eminence contain a high density of both TIP39 and PTH2R fibers and terminals [9].

Associations of TIP39 with chemical compounds

  • We report here, that the PTH2R terminals also contain vesicular glutamate transporter-2, and suggest that TIP39 terminals are ideally positioned to modulate glutamatergic influences on hypophysiotropic neurons [9].

Regulatory relationships of TIP39


Other interactions of TIP39

  • Despite different primary structures, the secondary structures of PTH, PTHrP and TIP39 are quite similar [10].
  • Receptor-G-protein interaction increases the receptor binding selectivity of PTHrP and TIP39 [10].
  • To investigate the anatomical basis of suggestions that TIP39 affects the secretion of several hypophysiotropic hormones we performed double-labeling studies and found that only somatostatin fibers contain PTH2R in the median eminence, which suggests that somatostatin release could be directly regulated via the PTH2R [9].

Analytical, diagnostic and therapeutic context of TIP39


  1. New members of the parathyroid hormone/parathyroid hormone receptor family: the parathyroid hormone 2 receptor and tuberoinfundibular peptide of 39 residues. Usdin, T.B., Wang, T., Hoare, S.R., Mezey, E., Palkovits, M. Frontiers in neuroendocrinology. (2000) [Pubmed]
  2. Structure of tuberoinfundibular peptide of 39 residues. Piserchio, A., Usdin, T., Mierke, D.F. J. Biol. Chem. (2000) [Pubmed]
  3. Agonist-specific regulation of parathyroid hormone (PTH) receptor type 2 activity: structural and functional analysis of PTH- and tuberoinfundibular peptide (TIP) 39-stimulated desensitization and internalization. Bisello, A., Manen, D., Pierroz, D.D., Usdin, T.B., Rizzoli, R., Ferrari, S.L. Mol. Endocrinol. (2004) [Pubmed]
  4. PTH2 receptor-mediated inhibitory effect of parathyroid hormone and TIP39 on cell proliferation. Misiano, P., Scott, B.B., Scheideler, M.A., Garnier, M. Eur. J. Pharmacol. (2003) [Pubmed]
  5. Identification and characterization of the zebrafish and fugu genes encoding tuberoinfundibular peptide 39. Papasani, M.R., Gensure, R.C., Yan, Y.L., Gunes, Y., Postlethwait, J.H., Ponugoti, B., John, M.R., Jüppner, H., Rubin, D.A. Endocrinology (2004) [Pubmed]
  6. Differential expression of tuberoinfundibular peptide 38 and glucose-6-phosphatase in tilapia. Shoemaker, J.M., Riley, L.G., Hirano, T., Grau, E.G., Rubin, D.A. Gen. Comp. Endocrinol. (2006) [Pubmed]
  7. Postnatal development and gender-dependent expression of TIP39 in the rat brain. Dobolyi, A., Wang, J., Irwin, S., Usdin, T.B. J. Comp. Neurol. (2006) [Pubmed]
  8. Neurons containing tuberoinfundibular peptide of 39 residues are activated following male sexual behavior. Wang, J., Coolen, L.M., Brown, J.L., Usdin, T.B. Neuropeptides (2006) [Pubmed]
  9. The distribution and neurochemistry of the parathyroid hormone 2 receptor in the rat hypothalamus. Dobolyi, A., Irwin, S., Wang, J., Usdin, T.B. Neurochem. Res. (2006) [Pubmed]
  10. Molecular mechanisms of ligand recognition by parathyroid hormone 1 (PTH1) and PTH2 receptors. Hoare, S.R., Usdin, T.B. Curr. Pharm. Des. (2001) [Pubmed]
  11. Emerging functions for tuberoinfundibular peptide of 39 residues. Usdin, T.B., Dobolyi, A., Ueda, H., Palkovits, M. Trends Endocrinol. Metab. (2003) [Pubmed]
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