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Neuroanatomy of Tuberoinfundibular Peptide 39 Related to Neuroendocrine and Behavioral Regulations

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Neuroanatomy of Neuroendocrine Systems

Part of the book series: Masterclass in Neuroendocrinology ((MANEURO,volume 12))

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Abstract

Tuberoinfundibular peptide of 39 residues (TIP39), also referred to as parathyroid hormone 2 (PTH2), is the endogenous ligand for the parathyroid hormone 2 receptor. TIP39 is synthesized by neurons in three small and distinct brain regions. These neurons project to discrete regions distributed throughout the brain, with highest abundance in the hypothalamus, lateral septum, medial prefrontal cortex, amygdala, periaqueductal gray, nucleus of the solitary tract, locus coeruleus, and spinal cord dorsal horn. Neurons that express the PTH2 receptor are present in each of the regions to which TIP39 neurons project. Experiments have been carried out to evaluate the potential contribution of TIP39-PTH2 receptor signaling to functions thought to be influenced by circuits in regions with high TIP39/PTH2 receptor density. Current evidence supports a role for this peptide/receptor system in multiple homeostatic responses or adaptations, including to nociceptive stimuli, changes in environmental temperature, threat, maternal function, and social awareness.

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Acknowledgements and Funding

The work was supported by the Hungarian National Research, Development and Innovation Office OTKA K134221, NKFIH-4300-1/2017-NKP_17 research grants, Eötvös Loránd University Thematic Excellence Programme 2020 (TKP2020-IKA-05) supported by the National Research, Development and Innovation Office. Research in the laboratory of Dr. Usdin was supported by the Intramural Research Program of the National Institute of Mental Health (ZIC MH002963-04).

Key References

  • Anneser, L., Alcantara, I.C., Gemmer, A., Mirkes, K., Ryu, S. and Schuman, E.M. (2020). The neuropeptide Pth2 dynamically senses others via mechanosensation. Nature 588, 653–657. A breakthrough article about the social function of tuberoinfundibular peptide 39 in zebra fish.

  • Bridges, R.S. (2020). The behavioral neuroendocrinology of maternal behavior: Past accomplishments and future directions. Horm Behav 120, 104662. A recent review article about the current state of knowledge related to maternal behavior.

  • Cservenak, M., Keller, D., Kis, V., Fazekas, E.A., Ollos, H., Leko, A.H., Szabo, E.R., Renner, E., Usdin, T.B., Palkovits, M., Dobolyi A. (2017). A thalamo-hypothalamic pathway that activates oxytocin neurons in social contexts in female rats. Endocrinology 158, 335–348. The potential involvement of TIP39 in the control of paraventricular oxytocin neurons is presented.

  • Cservenak, M., Szabo, E.R., Bodnar, I., Leko, A., Palkovits, M., Nagy, G.M., Usdin, T.B. and Dobolyi, A. (2013). Thalamic neuropeptide mediating the effects of nursing on lactation and maternal motivation. Psychoneuroendocrinology 38, 3070–3084. The article presents evidence on the role of TIP39 in prolactin release and also in the control of maternal behaviors.

  • Dimitrov, E.L., Kim, Y.Y. and Usdin, T.B. (2011). Regulation of hypothalamic signaling by tuberoinfundibular peptide of 39 residues is critical for the response to cold: a novel peptidergic mechanism of thermoregulation. J Neurosci 31, 18166–18179. Description of the thermoregulatory function of TIP39.

  • Dimitrov, E.L., Kuo, J., Kohno, K. and Usdin, T.B. (2013). Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues. Proc Natl Acad Sci U S A 110, 13156–13161. The nociceptive function of TIP39 at the supraspinal level is described.

  • Dobolyi, A., Cservenak, M. and Young, L.J. (2018). Thalamic integration of social stimuli regulating parental behavior and the oxytocin system. Front Neuroendocrinol 51, 102–115. A review article about the involvement of the neuronal pathway containing TIP39 in social interactions.

  • Dobolyi, A., Ueda, H., Uchida, H., Palkovits, M. and Usdin, T.B. (2002). Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception. Proc Natl Acad Sci U S A 99, 1651–1656. This paper reports the cloning of TIP39 and also its role in nociceptive information transfer at the level of the spinal cord.

  • Numan, M. (2020). The Parental Brain. Oxford University Press. The book includes current knowledge about maternal and paternal behavioral changes as well as endocrine alterations.

  • Phillipps, H.R., Yip, S.H. and Grattan, D.R. (2020). Patterns of prolactin secretion. Mol Cell Endocrinol 502, 110,679. The control of prolactin secretion is presented in this recent review, which also includes the role of TIP39 in the central regulation of prolactin release.

  • Tsuda, M.C., Yeung, H.M., Kuo, J. and Usdin, T.B. (2015). Incubation of Fear Is Regulated by TIP39 Peptide Signaling in the Medial Nucleus of the Amygdala. J Neurosci 35, 12152–12161. In his paper how TIP39 affects fear processing is presented.

  • Usdin, T.B., Gruber, C. and Bonner, T.I. (1995). Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. J Biol Chem 270, 15455–15458. This is the original paper, in which the cloning of parathyroid hormone 2 receptor was reported.

  • Usdin, T.B., Hoare, S.R., Wang, T., Mezey, E. and Kowalak, J.A. (1999). TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci 2, 941–943. The identification of TIP39 purified from bovine hypothalamus was reported in this seminal paper in the field.

  • Varga, T., Palkovits, M., Usdin, T.B. and Dobolyi, A. (2008). The medial paralemniscal nucleus and its afferent neuronal connections in rat. J Comp Neurol 511, 221–237. One of the three regions where TIP39 is expressed is the medial paralemniscal nucleus. The available knowledge about these TIP39-expressing neurons is limited, however, their connections with the brain auditory systems havecontrast to the profoundly different localization of been determined in this paper.

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Authors and Affiliations

  1. MTA-ELTE Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Eötvös Loránd Research Network and Eötvös Loránd University, Budapest, Hungary

    Árpád Dobolyi

  2. Systems Neuroscience Imaging Resource, National Institute of Mental Health, NIH, Bethesda, MD, USA

    Ted B. Usdin

  3. National Institute of Mental Health, Intramural Research Program, NIH, Bethesda, MD, USA

    Ted B. Usdin

Authors
  1. Árpád Dobolyi
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  2. Ted B. Usdin
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Corresponding authors

Correspondence to Árpád Dobolyi or Ted B. Usdin .

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Editors and Affiliations

  1. Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Baden-Württemberg, Germany

    Valery Grinevich

  2. Department of Physiology & Neurobiology, Eötvös Loránd University, Budapest, Hungary

    Árpád Dobolyi

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Dobolyi, Á., Usdin, T.B. (2021). Neuroanatomy of Tuberoinfundibular Peptide 39 Related to Neuroendocrine and Behavioral Regulations. In: Grinevich, V., Dobolyi, Á. (eds) Neuroanatomy of Neuroendocrine Systems. Masterclass in Neuroendocrinology, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-030-86630-3_14

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