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

• PTH2 receptor-mediated inhibitory effect of parathyroid hormone and TIP39 on cell proliferation [4].
• The fugu TIP39 precursor was encoded by a gene comprising at least three exons [5].
• Using degenerate primers based on conserved zebrafish and fugu TIP39 nucleotide sequences, 3'-RACE reactions isolated the coding region of a putative TIP38 cDNA in the Nile tilapia (Oreochromis niloticus) [6].
• The appearance of TIP39 during early, and decline during late, postnatal development together with the gender-dependent levels in mature animals suggests that TIP39 may play a role in sexual maturation or gender-specific functions [7].
• To test this hypothesis, we examined induction of Fos in TIP39 containing neurons in the mSPFp following male sexual behavior [8].

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

• The PTH2 receptor is activated by TIP39 but not by PTHrP [10].

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

• Treatment of hypothalamic explants with TIP39, and intraventricular injection of the peptide, suggest that it might stimulate hypothalamic-releasing factor secretion [11].
• Injection of TIP39, and sequestration of endogenous TIP39 by intrathecal injection of an antibody to TIP39, have provided evidence that it is involved in some aspects of pain sensitivity [11].
• In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT-PCR, and immunocytochemistry [7].

References