Abstract
Thyroid hormones play an important role in regulating seasonal adaptations of mammals. Several studies suggested that reduced availability of 3,3′,5-triiodothyronine (T3) in the hypothalamus is required for the physiological adaptation to winter in Djungarian hamsters. We have previously shown that T3 is involved in the regulation of daily torpor, but it remains unclear, whether T3 affects torpor by central or peripheral mechanisms. To determine the effect of T3 concentrations within the hypothalamus in regulating daily torpor, we tested the hypothesis that low hypothalamic T3 metabolism would favour torpor and high T3 concentrations would not. In experiment 1 gene expression in torpid hamsters was assessed for transporters carrying thyroid hormones between cerebrospinal fluid and hypothalamic cells and for deiodinases enzymes, activating or inactivating T3 within hypothalamic cells. Gene expression analysis suggests reduced T3 in hypothalamic cells during torpor. In experiment 2, hypothalamic T3 concentrations were altered via microdialysis and torpor behaviour was continuously monitored by implanted body temperature transmitters. Increased T3 concentrations in the hypothalamus reduced expression of torpor as well as torpor bout duration and depth. Subsequent analysis of gene expression in the ependymal layer of the third ventricle showed clear up-regulation of T3 inactivating deiodinase 3 but no changes in several other genes related to photoperiodic adaptations in hamsters. Finally, serum analysis revealed that increased total T3 serum concentrations were not necessary to inhibit torpor expression. Taken together, our results are consistent with the hypothesis that T3 availability within the hypothalamus significantly contributes to the regulation of daily torpor via a central pathway.
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Abbreviations
- ARC:
-
Arcuate nucleus
- BAT:
-
Brown adipose tissue
- CRBP1:
-
Cellular retinol-binding protein 1
- DIO:
-
Deiodinase (type 2 or 3)
- GPR50:
-
G protein-coupled receptor 50
- H3R:
-
Histamine receptor 3
- LP:
-
Long photoperiod
- MCT8:
-
Monocarboxylate transporter 8
- OATP1c1:
-
Organic anion transporter polypeptide-related protein 1c1
- PVN:
-
Paraventricular nucleus
- SP:
-
Short photoperiod
- SRIF:
-
Somatotropin release-inhibiting factor
- T3:
-
Triiodothyronine
- T4:
-
Thyroxine
- T b :
-
Body temperature
- TRH:
-
Thyrotropin-releasing hormone
- TSH:
-
Thyroid-stimulating hormone
- VMH:
-
Ventromedial hypothalamus
- ZT:
-
Zeitgebertime
References
Bank JHH, Kemmling J, Rijntjes E et al (2015) Thyroid hormone status affects expression of daily torpor and gene transcription in Djungarian hamsters (Phodopus sungorus). Horm Behav 75:120–129. doi:10.1016/j.yhbeh.2015.09.006
Barrett P, Ross AW, Balik A et al (2005) Photoperiodic regulation of histamine H3 receptor and VGF messenger ribonucleic acid in the arcuate nucleus of the Siberian hamster. Endocrinology 146:1930–1939. doi:10.1210/en.2004-1452
Barrett P, Ivanova E, Graham ES et al (2006) 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 191:687–698. doi:10.1677/joe.1.06929
Barrett P, Ebling FJP, Schuhler S et al (2007) Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction. Endocrinology 148:3608–3617. doi:10.1210/en.2007-0316
Barrett P, van den Top M, Wilson D et al (2009) Short photoperiod-induced decrease of histamine H3 receptors facilitates activation of hypothalamic neurons in the Siberian hamster. Endocrinology 150:3655–3663. doi:10.1210/en.2008-1620
Bechtold DA, Sidibe A, Saer BRC, et al (2012) A role for the melatonin-related receptor GPR50 in leptin signaling, adaptive thermogenesis, and torpor. Curr Biol CB 22:70–77. doi:10.1016/j.cub.2011.11.043
Bianco AC, Salvatore D, Gereben B et al (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23:38–89. doi:10.1210/edrv.23.1.0455
Bolborea M, Laran-Chich MP, Rasri K et al (2011) Melatonin controls photoperiodic changes in tanycyte vimentin and neural cell adhesion molecule expression in the Djungarian hamster (Phodopus sungorus). Endocrinology 152:3871–3883. doi:10.1210/en.2011-1039
Braulke LJ, Heldmaier G (2010) Torpor and ultradian rhythms require an intact signalling of the sympathetic nervous system. Cryobiology 60:198–203. doi:10.1016/j.cryobiol.2009.11.001
Brazeau P, Vale W, Burgus R et al (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79
Choi W-H, Ji K-A, Jeon S-B et al (2005) Anti-inflammatory roles of retinoic acid in rat brain astrocytes: suppression of interferon-gamma-induced JAK/STAT phosphorylation. Biochem Biophys Res Commun 329:125–131. doi:10.1016/j.bbrc.2005.01.110
Contreras C, Gonzalez F, Fernø J et al (2015) The brain and brown fat. Ann Med 47:150–168. doi:10.3109/07853890.2014.919727
Crisanti P, Omri B, Hughes E et al (2001) The expression of thyrotropin receptor in the brain. Endocrinology 142:812–822. doi:10.1210/endo.142.2.7943
Davis PJ, Goglia F, Leonard JL (2016) Nongenomic actions of thyroid hormone. Nat Rev Endocrinol 12:111–121. doi:10.1038/nrendo.2015.205 (review)
Diedrich V, Bank JH, Scherbarth F, Steinlechner S (2015) Torpor expression in juvenile and adult Djungarian hamsters (Phodopus sungorus) differs in frequency, duration and onset in response to a daily cycle in ambient temperature. J Therm Biol 53:23–32. doi:10.1016/j.jtherbio.2015.08.006
Dong H, Zhang W, Zeng X et al (2014) Histamine induces upregulated expression of histamine receptors and increases release of inflammatory mediators from microglia. Mol Neurobiol 49:1487–1500. doi:10.1007/s12035-014-8697-6
Dumbell RA, Scherbarth F, Diedrich V et al (2015) Somatostatin agonist pasireotide promotes a physiological state resembling short-day acclimation in the photoperiodic male Siberian hamster (Phodopus sungorus). J Neuroendocrinol 27:588–599. doi:10.1111/jne.12289
Franklin K, Paxinos G (2008) The mouse brain in sterotactic coordinates, 3rd edn. Academic Press, San Diego
Hanon EA, Lincoln GA, Fustin J-M, et al (2008) Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr Biol CB 18:1147–1152. doi:10.1016/j.cub.2008.06.076
Heldmaier G, Ruf T (1992) Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B 162:696–706.
Heldmaier G, Steinlechner S (1981a) Seasonal control of energy requirements for thermoregulation in the Djungarian hamster (Phodopus sungorus), living in natural photoperiod. J Comp Physiol B 142:429–437
Heldmaier G, Steinlechner S (1981b) Seasonal pattern and energetics of short daily torpor in the Djungarian hamster, Phodopus sungorus. Oecologia 48:265–270
Heldmaier G, Klingenspor M, Werneyer M et al (1999) Metabolic adjustments during daily torpor in the Djungarian hamster. Am J Physiol 276:E896–E906
Heldmaier G, Ortmann S, Elvert R (2004) Natural hypometabolism during hibernation and daily torpor in mammals. Respir Physiol Neurobiol 141:317–329. doi:10.1016/j.resp.2004.03.014
Herwig A, Wilson D, Logie TJ et al (2009) Photoperiod and acute energy deficits interact on components of the thyroid hormone system in hypothalamic tanycytes of the Siberian hamster. Am J Physiol Regul Integr Comp Physiol 296:R1307–R1315. doi:10.1152/ajpregu.90755.2008
Herwig A, Petri I, Barrett P (2012) Hypothalamic gene expression rapidly changes in response to photoperiod in juvenile Siberian hamsters (Phodopus sungorus). J Neuroendocrinol 24:991–998. doi:10.1111/j.1365-2826
Herwig A, de Vries EM, Bolborea M, et al (2013) Hypothalamic ventricular ependymal thyroid hormone deiodinases are an important element of circannual timing in the Siberian hamster (Phodopus sungorus). PloS One 8:e62003. doi:10.1371/journal.pone.0062003
Himms-Hagen J (1984) Nonshivering thermogenesis. Brain Res Bull 12:151–160
Jethwa PH, Barrett P, Turnbull Y et al (2009) The role of histamine 3 receptors in the control of food intake in a seasonal model of obesity: the Siberian hamster. Behav Pharmacol 20:155–165. doi:10.1097/FBP.0b013e32832a8099
Kameda Y, Arai Y, Nishimaki T (2003) Ultrastructural localization of vimentin immunoreactivity and gene expression in tanycytes and their alterations in hamsters kept under different photoperiods. Cell Tissue Res 314:251–262. doi:10.1007/s00441-003-0789-y
Knopper LD, Boily P (2000) The energy budget of captive Siberian hamsters, Phodopus sungorus, exposed to photoperiod changes: mass loss is caused by a voluntary decrease in food intake. Physiol Biochem Zool PBZ 73:517–522. doi:10.1086/317730
Köhrle J (1999) Local activation and inactivation of thyroid hormones: the deiodinase family. Mol Cell Endocrinol 151:103–119.
Kozai TDY, Jaquins-Gerstl AS, Vazquez AL et al (2015) Brain tissue responses to neural implants impact signal sensitivity and intervention strategies. ACS Chem Neurosci 6:48–67. doi:10.1021/cn500256e
Lewis JE, Brameld JM, Hill P et al (2016) Thyroid hormone and vitamin D regulate VGF expression and promoter activity. J Mol Endocrinol 56:123–134. doi:10.1530/JME-15-0224
Martinez de Mena R, Scanlan TS, Obregon M-J (2010) The T3 receptor beta1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes. Endocrinology 151:5074–5083. doi:10.1210/en.2010-0533
Murphy M, Jethwa PH, Warner A et al (2012) Effects of manipulating hypothalamic triiodothyronine concentrations on seasonal body weight and torpor cycles in Siberian hamsters. Endocrinology 153:101–112. doi:10.1210/en.2011-1249
Pekny M, Wilhelmsson U, Bogestål YR, Pekna M (2007) The role of astrocytes and complement system in neural plasticity. Int Rev Neurobiol 82:95–111. doi:10.1016/S0074-7742(07)82005-8
Petri I, Diedrich V, Wilson D, et al (2016) Orchestration of gene expression across the seasons: hypothalamic gene expression in natural photoperiod throughout the year in the Siberian hamster. Sci Rep 6:29689. doi:10.1038/srep29689
Rodrigues NC, da Cruz NS, de Paula Nascimento C et al (2015) Sleep deprivation alters thyroid hormone economy in rats. Exp Physiol 100:193–202. doi:10.1113/expphysiol.2014.083303
Ross AW, Webster CA, Mercer JG et al (2004) Photoperiodic regulation of hypothalamic retinoid signaling: association of retinoid X receptor gamma with body weight. Endocrinology 145:13–20. doi:10.1210/en.2003-0838
Ross AW, Bell LM, Littlewood PA et al (2005) Temporal changes in gene expression in the arcuate nucleus precede seasonal responses in adiposity and reproduction. Endocrinology 146:1940–1947. doi:10.1210/en.2004-1538
Ross AW, Johnson CE, Bell LM et al (2009) Divergent regulation of hypothalamic neuropeptide Y and agouti-related protein by photoperiod in F344 rats with differential food intake and growth. J Neuroendocrinol 21:610–619. doi:10.1111/j.1365-2826.2009.01878.x
Ross AW, Helfer G, Russell L, et al (2011) Thyroid hormone signalling genes are regulated by photoperiod in the hypothalamus of F344 rats. PloS One 6:e21351. doi:10.1371/journal.pone.0021351
Ruf T, Heldmaier G (1992) The impact of daily torpor on energy requirements in the Djungarian hamster, Phodopus sungorus. Physiol Zool 65:994–1010
Ruf T, Steinlechner S, Heldmaier G (1989) Rhythmicity of body temperature and torpor in the Djungarian hamster, Phodopus sungorus. In: Malan A, Canguilhem B (eds) Living in the cold II. John Libbey Eurotext, London, pp 53–61
Ruf T, Klingenspor M, Preis H, Heldmaier G (1991) Daily torpor in the Djungarian hamster (Phodopus sungorus): interactions with food intake, activity, and social behaviour. J Comp Physiol B 160:609–615. doi:10.1007/BF00571257
Sánchez E, Vargas MA, Singru PS et al (2009) Tanycyte pyroglutamyl peptidase II contributes to regulation of the hypothalamic–pituitary–thyroid axis through glial–axonal associations in the median eminence. Endocrinology 150:2283–2291. doi:10.1210/en.2008-1643
Scherbarth F, Diedrich V, Dumbell RA et al (2015) Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal. Am J Physiol Regul Integr Comp Physiol. doi:10.1152/ajpregu.00191.2015
Schroeder AC, Privalsky ML (2014) Thyroid hormones, T3 and T4, in the brain. Front Endocrinol 5:40. doi:10.3389/fendo.2014.00040
Watanabe M, Yasuo S, Watanabe T et al (2004) Photoperiodic regulation of type 2 deiodinase gene in Djungarian hamster: possible homologies between avian and mammalian photoperiodic regulation of reproduction. Endocrinology 145:1546–1549. doi:10.1210/en.2003-1593
Werneck de Castro JP, Fonseca TL, Ueta CB et al (2015) Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine. J Clin Invest 125:769–781. doi:10.1172/JCI77588
Wirth EK, Schweizer U, Köhrle J (2014) Transport of thyroid hormone in brain. Front Endocrinol 5:98. doi:10.3389/fendo.2014.00098
Wittmann G, Szabon J, Mohácsik P et al (2015) Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and after endotoxemia at the blood–brain barrier of male rodents. Endocrinology 156:1552–1564. doi:10.1210/en.2014-1830
Zhang Z, Bisschop P, Foppen E et al (2016) A model for chronic, intrahypothalamic thyroid hormone administration in the rat. J Endocrinol. doi:10.1530/JOE-15-0501
Acknowledgements
This work was financially supported by the German Research Foundation (DFG, Emmy-Noether HE6383/1 to AH) and the British Society for Neuroendocrinology (Research Grant to JB).
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Communicated by F. Breukelen.
This manuscript is part of the special issue Hibernation—Guest Editors: Frank van Breukelen and Jenifer C. Utz.
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Bank, J.H.H., Cubuk, C., Wilson, D. et al. Gene expression analysis and microdialysis suggest hypothalamic triiodothyronine (T3) gates daily torpor in Djungarian hamsters (Phodopus sungorus). J Comp Physiol B 187, 857–868 (2017). https://doi.org/10.1007/s00360-017-1086-5
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DOI: https://doi.org/10.1007/s00360-017-1086-5