The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and
                    the Possibilities for Their Genetic Manipulation

Helge Müller-Fielitz; Markus Schwaninger

doi:10.1055/a-1065-1855

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 2020; 128(06/07): 388-394
DOI: 10.1055/a-1065-1855

Mini-Review

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

Authors

Helge Müller-Fielitz

¹Institute for Experimental and Clinical Pharmacology and Toxicology, Lübeck, University of Lübeck, Germany
Markus Schwaninger

¹Institute for Experimental and Clinical Pharmacology and Toxicology, Lübeck, University of Lübeck, Germany

Abstract

Thyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3^rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

Keywords

tanycytes - TRH - HPT axis - genetic tools - viral vectors - transgenic mice

Volltext

Referenzen

References
1 Johann K, Cremer AL, Fischer AW. et al. Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption. Cell Rep 2019; 27: 3385-3400 e3383.
2 Martinez-Sanchez N, Seoane-Collazo P, Contreras C. et al. Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance. Cell Metab 2017; 26: 212-229 e212.
3 Tsourdi E, Rijntjes E, Kohrle J. et al. Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1. Endocrinology 2015; 156: 3517-3527
4 Pantos CI, Malliopoulou VA, Mourouzis IS. et al. Long-term thyroxine administration protects the heart in a pattern similar to ischemic preconditioning. Thyroid 2002; 12: 325-329.
5 Harder L, Dudazy-Gralla S, Muller-Fielitz H. et al. Maternal Thyroid Hormone is Required for Parvalbumin Neuron Development in the Anterior Hypothalamic Area. J Neuroendocrinol 2018;
6 Mayerl S, Muller J, Bauer R. et al. Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. The Journal of clinical investigation 2014; 124: 1987-1999.
7 Stepien BK, Huttner WB.. Transport, Metabolism, and Function of Thyroid Hormones in the Developing Mammalian Brain. Front Endocrinol (Lausanne) 2019; 10: 209.
8 Cyr NE, Stuart RC, Zhu X. et al. Biosynthesis of proTRH-derived peptides in prohormone convertase 1 and 2 knockout mice. Peptides 2012; 35: 42-48
9 Joseph-Bravo P, Jaimes-Hoy L, Charli JL. Advances in TRH signaling. Rev Endocr Metab Disord 2016; 17: 545-558.
10 Joseph-Bravo P, Jaimes-Hoy L, Charli J-L. Regulation of TRH neurons and energy homeostasis-related signals under stress. Journal of Endocrinology 2015; 224: R139-R159.
11 Kadar A, Sanchez E, Wittmann G. et al. Distribution of hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons in the hypothalamic paraventricular nucleus of the mouse. The Journal of comparative neurology 2010; 518: 3948-3961.
12 Weintraub BD, Gesundheit N, Taylor T. et al. Effect of TRH on TSH glycosylation and biological action. Ann N Y Acad Sci 1989; 553: 205-213.
13 Rodriguez EM, Blazquez JL, Pastor FE. et al. Hypothalamic tanycytes: a key component of brain-endocrine interaction. Int Rev Cytol 2005; 247: 89-164.
14 Rodriguez E, Guerra M, Peruzzo B. et al. Tanycytes: a rich morphological history to underpin future molecular and physiological investigations. J Neuroendocrinol 2019; e12690.
15 Morita-Takemura S, Wanaka A. Blood-to-brain communication in the hypothalamus for energy intake regulation. Neurochemistry international 2019; 128: 135-142.
16 Mullier A, Bouret SG, Prevot V. et al. Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain. The Journal of comparative neurology 2010; 518: 943-962.
17 Wittmann G, Farkas E, Szilvasy-Szabo A. et al. Variable proopiomelanocortin expression in tanycytes of the adult rat hypothalamus and pituitary stalk. The Journal of comparative neurology 2017; 525: 411-441
18 Campbell JN, Macosko EZ, Fenselau H. et al. A molecular census of arcuate hypothalamus and median eminence cell types. Nature neuroscience 2017; 20: 484-496.
19 Tu HM, Kim SW, Salvatore D. et al. Regional distribution of type 2 thyroxine deiodinase messenger ribonucleic acid in rat hypothalamus and pituitary and its regulation by thyroid hormone. Endocrinology 1997; 138: 3359-3368.
20 Muller J, Heuer H. Expression pattern of thyroid hormone transporters in the postnatal mouse brain. Front Endocrinol (Lausanne) 2014; 5: 92.
21 Roberts LM, Woodford K, Zhou M. et al. Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier. Endocrinology 2008; 149: 6251-6261
22 Fekete C, Lechan RM. Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocrine reviews 2014; 35: 159-194.
23 Kakucska I, Rand W, Lechan RM. Thyrotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is dependent upon feedback regulation by both triiodothyronine and thyroxine. Endocrinology 1992; 130: 2845-2850.
24 Fonseca TL, Correa-Medina M, Campos MP. et al. Coordination of hypothalamic and pituitary T3 production regulates TSH expression. The Journal of clinical investigation 2013; 123: 1492-1500.
25 Shioda S, Nakai Y. Immunocytochemical localization of TRH and autoradiographic determination of 3H-TRH-binding sites in the arcuate nucleus-median eminence of the rat. Cell Tissue Res 1983; 228: 475-487
26 Müller-Fielitz H, Stahr M, Bernau M. et al. Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis. Nature communications 2017; 8: 484.
27 Rodriguez-Rodriguez A, Lazcano I, Sanchez-Jaramillo E. et al. Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux Into Portal Capillaries. Front Endocrinol (Lausanne) 2019; 10: 401.
28 Bauer K. Inactivation of thyrotropin-releasing hormone (TRH) by the hormonally regulated TRH-degrading ectoenzyme A potential regulator of TRH signals?. Trends in endocrinology and metabolism: TEM 1995; 6: 101-105
29 Sanchez E, Vargas MA, Singru PS. et al. Tanycyte pyroglutamyl peptidase II contributes to regulation of the hypothalamic-pituitary-thyroid axis through glial-axonal associations in the median eminence. Endocrinology 2009; 150: 2283-2291.
30 Marsili A, Sanchez E, Singru P. et al. Thyroxine-induced expression of pyroglutamyl peptidase II and inhibition of TSH release precedes suppression of TRH mRNA and requires type 2 deiodinase. J Endocrinol 2011; 211: 73-78
31 Jean-Louis Charli D, Cote-Velez Antonieta, Adair Rodriguez-Rodriguez. et al. Thyrotropin-Releasing Hormone-Degrading Ectoenzyme Controls Thyrotropin Secretion and Body Weight in Male Rodents. In, Journal of the Endocrine Society 2019; SUN-465
32 Schomburg L, Bauer K. Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme. Endocrinology 1995; 136: 3480-3485
33 Alvarez-Salas E, Alcantara-Alonso V, Matamoros-Trejo G. et al. Mediobasal hypothalamic and adenohypophyseal TRH-degrading enzyme (PPII) is down-regulated by zinc deficiency. International journal of developmental neuroscience : the official journal of the International Society for. Developmental Neuroscience 2015; 46: 115-124.
34 Xu Y, Tamamaki N, Noda T. et al. Neurogenesis in the ependymal layer of the adult rat 3rd ventricle. Exp Neurol 2005; 192: 251-264
35 Barrett P, Ivanova E, Graham ES. et al. Photoperiodic regulation of cellular retinol binding protein, CRBP1 [corrected] and nestin in tanycytes of the third ventricle ependymal layer of the Siberian hamster. J Endocrinol 2006; 191: 687-698.
36 Klimova L, Lachova J, Machon O. et al. Generation of mRx-Cre transgenic mouse line for efficient conditional gene deletion in early retinal progenitors. PLoS One 2013; 8: e63029
37 Miranda-Angulo AL, Byerly MS, Mesa J. et al. Rax regulates hypothalamic tanycyte differentiation and barrier function in mice. The Journal of comparative neurology 2014; 522: 876-899
38 Orquera DP, Nasif S, Low MJ. et al. Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus. Dev Biol 2016; 416: 212-224.
39 Li J, Tang Y, Cai D. IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nature cell biology 2012; 14: 999-1012.
40 Balordi F, Fishell G. Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal. J Neurosci 2007; 27: 14248-14259.
41 Lee DA, Bedont JL, Pak T. et al. Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nature neuroscience 2012; 15: 700-702.
42 Pak T, Yoo S, Miranda-Angulo AL. et al. Rax-CreERT2 knock-in mice: a tool for selective and conditional gene deletion in progenitor cells and radial glia of the retina and hypothalamus. PLoS One 2014; 9: e90381.
43 Salvatierra J, Lee DA, Zibetti C. et al. The LIM homeodomain factor Lhx2 is required for hypothalamic tanycyte specification and differentiation. J Neurosci 2014; 34: 16809-16820.
44 Yoo S, Cha D, Kim DW. et al. Tanycyte-Independent Control of Hypothalamic Leptin Signaling. Front Neurosci 2019; 13: 240
45 Kaminskas B, Goodman T, Hagan A. et al. Characterisation of endogenous players in fibroblast growth factor-regulated functions of hypothalamic tanycytes and energy-balance nuclei. J Neuroendocrinol 2019; e12750.
46 Robins SC, Stewart I, McNay DE. et al. alpha-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nature communications 2013; 4: 2049.
47 Haan N, Goodman T, Najdi-Samiei A. et al. Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J Neurosci 2013; 33: 6170-6180.
48 Berger UV, Hediger MA. Differential distribution of the glutamate transporters GLT-1 and GLAST in tanycytes of the third ventricle. The Journal of comparative neurology 2001; 433: 101-114
49 Redecker P. Postnatal development of glial fibrillary acidic protein (GFAP) immunoreactivity in pituicytes and tanycytes of the Mongolian gerbil (Meriones unguiculatus). Histochemistry 1989; 91: 507-515
50 Mori T, Tanaka K, Buffo A. et al. Inducible gene deletion in astroglia and radial glia--a valuable tool for functional and lineage analysis. Glia 2006; 54: 21-34.
51 Hirrlinger PG, Scheller A, Braun C. et al. Temporal control of gene recombination in astrocytes by transgenic expression of the tamoxifen-inducible DNA recombinase variant CreERT2. Glia 2006; 54: 11-20.
52 Rottkamp DM, Rudenko IA, Maier MT. et al. Leptin potentiates astrogenesis in the developing hypothalamus. Molecular metabolism 2015; 4: 881-889
53 de Vries EM, Nagel S, Haenold R. et al. The Role of Hypothalamic NF-kappaB Signaling in the Response of the HPT-Axis to Acute Inflammation in Female Mice. Endocrinology 2016; 157: 2947-2956.
54 Hofmann K, Lamberz C, Piotrowitz K. et al. Tanycytes and a differential fatty acid metabolism in the hypothalamus. Glia 2016;
55 Garcia AD, Doan NB, Imura T. et al. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nature neuroscience 2004; 7: 1233-1241.
56 Bouyakdan K, Martin H, Lienard F. et al. The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system. The Journal of clinical investigation 2019; 130.
57 Budry L, Bouyakdan K, Tobin S. et al. DBI/ACBP loss-of-function does not affect anxiety-like behaviour but reduces anxiolytic responses to diazepam in mice. Behavioural brain research 2016; 313: 201-207
58 Zhuo L, Theis M, Alvarez-Maya I. et al. hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo. Genesis (New York, NY : 2000) 2001; 31: 85-94
59 Mirzadeh Z, Kusne Y, Duran-Moreno M. et al. Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories. Nature communications 2017; 8: 13759
60 Faubel R, Westendorf C, Bodenschatz E. et al. Cilia-based flow network in the brain ventricles. Science 2016; 353: 176-178
61 Peitz M, Pfannkuche K, Rajewsky K. et al. Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: a tool for efficient genetic engineering of mammalian genomes. Proc Natl Acad Sci U S A 2002; 99: 4489-4494.
62 Parkash J, Messina A, Langlet F. et al. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence. Nature communications 2015; 6: 6385.
63 Langlet F, Levin BE, Luquet S. et al. Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab 2013; 17: 607-617.
64 Geller S, Arribat Y, Netzahualcoyotzi C. et al. Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion. Cell Metab 2019; 30: 833-844.e837.
65 Zhang Y, Kim MS, Jia B. et al. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature 2017; 548: 52-57.
66 Elizondo-Vega R, Cortes-Campos C, Barahona MJ. et al. Inhibition of hypothalamic MCT1 expression increases food intake and alters orexigenic and anorexigenic neuropeptide expression. Sci Rep 2016; 6: 33606
67 Elizondo-Vega R, Oyarce K, Salgado M. et al. Inhibition of Hypothalamic MCT4 and MCT1-MCT4 Expressions Affects Food Intake and Alters Orexigenic and Anorexigenic Neuropeptide Expressions. Molecular neurobiology 2019;
68 Uranga RM, Millan C, Barahona MJ. et al. Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior. Sci Rep 2017; 7: 3697.
69 Barahona MJ, Llanos P, Recabal A. et al. Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior. Glia 2018; 66: 592-605.
70 Martinez F, Cifuentes M, Tapia JC. et al. The median eminence as the hypothalamic area involved in rapid transfer of glucose to the brain: functional and cellular mechanisms. Journal of molecular medicine (Berlin, Germany) 2019; 97: 1085-1097.
71 Cortes-Campos C, Elizondo R, Carril C. et al. MCT2 expression and lactate influx in anorexigenic and orexigenic neurons of the arcuate nucleus. PLoS One 2013; 8: e62532.
72 Frayling C, Britton R, Dale N. ATP-mediated glucosensing by hypothalamic tanycytes. The Journal of physiology 2011; 589: 2275-2286.
73 Liu B, Paton JF, Kasparov S. Viral vectors based on bidirectional cell-specific mammalian promoters and transcriptional amplification strategy for use in vitro and in vivo. BMC biotechnology 2008; 8: 49.
74 Hanon EA, Lincoln GA, Fustin JM. et al. Ancestral TSH mechanism signals summer in a photoperiodic mammal. Current biology : CB 2008; 18: 1147-1152.
75 Benford H, Bolborea M, Pollatzek E. et al. A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes. Glia 2017; 65: 773-789.
76 Herenu CB, Sonntag WE, Morel GR. et al. The ependymal route for insulin-like growth factor-1 gene therapy in the brain. Neuroscience 2009; 163: 442-447.
77 Krashes MJ, Koda S, Ye C. et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. The Journal of clinical investigation 2011; 121: 1424-1428.
78 Kim S, Kim N, Park S. et al. Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance. Autophagy 2019; 1-21.
79 Chen R, Wu X, Jiang L. et al. Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity. Cell Rep 2017; 18: 3227-3241.