News and Reviews The regulatory role of neurotensin on the hypothalamic–anterior pituitary axons: Emphasis on the control of thyroid-related functions Vasileios Stolakis, Konstantinos Kalafatakis, John Botis, Apostolos Zarros, Charis Liapi * Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece article info Article history: Received 29 June 2009 Accepted 30 September 2009 Available online 29 October 2009 Keywords: Neurotensin Receptors Pituitary Hypothalamus Thyroid Regulation abstract Neurotensin (NT) is a 13 amino acid neurohormone and/or neuromodulator, located in the synaptic ves- icles and released from the neuronal terminals in a calcium-dependent manner. This peptide is present among mammalian and nonmammalian species, mainly in the central nervous system and the gastroin- testinal tract. Due to its neuroendocrine activity, NT has been related to the pathophysiology of a series of disorders, such as schizophrenia, drug-abuse, Parkinson’s disease, cancer, stroke, eating disorders and other neurodegenerative conditions. Moreover, NT participates in the physiology of pain-induction, cen- tral blood pressure control and inflammation. NT also plays an important interactive role in all compo- nents of the hypothalamic–anterior pituitary circuit, which is mediated by an endocrine, paracrine or/ and autocrine manner, towards most of the anatomical regions that define this circuit. A considerable amount of data implicates NT in thyroid-related regulation through this circuit, the exact mechanisms of which should be further investigated for the potential development of more targeted approaches towards the treatment of thyroid-related endocrine diseases. The aim of this study was to provide an up-to-date review of the literature concerning the regulatory role of NT on the hypothalamic–anterior pituitary axons, with an emphasis on the control of thyroid-related functions. Ó 2009 Elsevier Ltd. All rights reserved. Contents 1. Introduction ........................................................................................................... 1 2. Participation of NT in the hypothalamic–anterior pituitary axons ................................................................ 2 2.1. NT and gonadal axis interaction...................................................................................... 2 2.2. NT and PRL interaction ............................................................................................. 3 2.3. NT and GH interaction ............................................................................................. 3 2.4. NT and adrenal axis interaction ...................................................................................... 3 3. Regulatory role of NT in the hypothalamic–anterior pituitary–thyroid axis ........................................................ 3 3.1. Regulatory role of NT in the hypothalamus and the anterior pituitary ....................................................... 3 3.2. Functional cooperation between NT and thyroid hormones ............................................................... 4 Acknowledgments ...................................................................................................... 5 References ............................................................................................................ 5 1. Introduction Neurotensin (NT) is a 13 amino acid neurohormone and/or neu- romodulator (Carraway and Leeman, 1973; Uhl and Snyder, 1976), that is located in the synaptic vesicles (Bayer et al., 1991) and is re- leased from the neuronal terminals in a calcium (Ca 2+ )-dependent manner (Kitabgi et al., 1990). This peptide and its receptors are present among mammalian and nonmammalian species, mainly in the central nervous system (CNS) and the gastrointestinal tract (GIT) (Table 1)(Reinecke, 1985). The subcellular metabolic cycle of NT involves a larger (169 amino acid) inactive precursor com- plex, the cleavage of which results in the activation of NT (Ville- neuve et al., 2002), as well as a series of endopeptidases (Checler, 1994; Vincent et al., 1994), which extracellularly terminate NT 0143-4179/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.npep.2009.09.005 * Corresponding author. Address: Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str, GR-11527, Athens, Greece. Tel.: +30 210 7462531; fax: +30 210 7462554. E-mail address: cliapi@med.uoa.gr (C. Liapi). Neuropeptides 44 (2010) 1–7 Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep