Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed.

[1]  M. Carotenuto,et al.  Anxiety and depression levels in prepubertal obese children: a case-control study , 2014, Neuropsychiatric disease and treatment.

[2]  T. Sakurai,et al.  Role of orexin in modulating arousal, feeding, and motivation , 2013, Front. Behav. Neurosci..

[3]  G. Plazzi,et al.  Narcolepsy during Childhood: An Update , 2015, Neuropediatrics.

[4]  E. Bixler,et al.  Leptin and hunger levels in young healthy adults after one night of sleep loss , 2010, Journal of sleep research.

[5]  Levothyroxine improves subjective sleepiness in a euthyroid patient with narcolepsy without cataplexy. , 2014, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[6]  M. Garzón,et al.  Hypocretin1/OrexinA‐containing axons innervate locus coeruleus neurons that project to the Rat medial prefrontal cortex. Implication in the sleep‐wakefulness cycle and cortical activation , 2011, Synapse.

[7]  S. Kalra,et al.  Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner. , 1998, Regulatory peptides.

[8]  E. Bixler,et al.  Sleep apnoea and the hypothalamic–pituitary–adrenal axis in men and women: effects of continuous positive airway pressure , 2015, European Respiratory Journal.

[9]  V. Luca,et al.  Sympathetic and hyperthermic reactions by orexin A: Role of cerebral catecholaminergic neurons , 2007, Regulatory Peptides.

[10]  C. Babiloni,et al.  Heart rate variability is reduced in underweight and overweight healthy adult women , 2017, Clinical physiology and functional imaging.

[11]  L. Capranica,et al.  Relationship between RPE and Blood Lactate after Fatiguing Handgrip Exercise in Taekwondo and Sedentary Subjects , 2015 .

[12]  Yan Zhu,et al.  A neural circuit for circadian regulation of arousal , 2001, Nature Neuroscience.

[13]  Luis de Lecea,et al.  Hypocretin-1 Modulates Rapid Eye Movement Sleep through Activation of Locus Coeruleus Neurons , 2000, The Journal of Neuroscience.

[14]  R. Lechan,et al.  Immunohistochemical localization of thyrotropin-releasing hormone in the rat hypothalamus and pituitary. , 1982, Endocrinology.

[15]  M. I. Smith,et al.  Orexin A activates locus coeruleus cell firing and increases arousal in the rat. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Irahara,et al.  Orexins, orexigenic hypothalamic neuropeptides, suppress the pulsatile secretion of luteinizing hormone in ovariectomized female rats. , 1999, Biochemical and biophysical research communications.

[17]  M. M. Taylor,et al.  Hypocretin/orexin suppresses corticotroph responsiveness in vitro. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[18]  Z. Fatahi,et al.  The electrical activity of hippocampal pyramidal neuron is subjected to descending control by the brain orexin/hypocretin system , 2015, Neurobiology of Learning and Memory.

[19]  E. Bixler,et al.  Gender differences in the association of sleep apnea and inflammation , 2015, Brain, Behavior, and Immunity.

[20]  M. Carotenuto,et al.  Acupressure therapy for insomnia in adolescents: a polysomnographic study , 2013, Neuropsychiatric disease and treatment.

[21]  A. Mahdi,et al.  Leptin level correlates with obesity and health related quality of life in obstructive sleep apnea syndrome patients. , 2015, The Indian journal of tuberculosis.

[22]  Giovanni Messina,et al.  Laterality of a second player position affects lateral deviation of basketball shooting , 2014, Journal of sports sciences.

[23]  S. Moebus,et al.  Thyroid-Stimulating Hormone and Mild Cognitive Impairment: Results of the Heinz Nixdorf Recall Study. , 2015, Journal of Alzheimer's disease : JAD.

[24]  Gerard A. Zitnik.  Control of arousal through neuropeptide afferents of the locus coeruleus , 2016, Brain Research.

[25]  E. Mignot,et al.  Chronic Oral Administration of CG-3703, a Thyrotropin Releasing Hormone Analog, Increases Wake and Decreases Cataplexy in Canine Narcolepsy , 2000, Neuropsychopharmacology.

[26]  H. Kohno,et al.  Intracranial injection of thyrotropin releasing hormone (TRH) suppresses starvation-induced feeding and drinking in rats , 1982, Pharmacology Biochemistry and Behavior.

[27]  E. Akbari,et al.  The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze , 2007, Peptides.

[28]  P. Vigário,et al.  Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes? , 2016, Endocrine journal.

[29]  H. Shinno,et al.  Effect of levothyroxine on prolonged nocturnal sleep time and excessive daytime somnolence in patients with idiopathic hypersomnia. , 2011, Sleep medicine.

[30]  S. Chieffi,et al.  Exercise Causes Muscle GLUT4 Translocation in an Insulin-Independent Manner , 2015 .

[31]  I. Arnulf,et al.  Eating disorder and metabolism in narcoleptic patients. , 2007, Sleep.

[32]  W. Börner,et al.  [Thyroid hormones]. , 1974, Die Medizinische Welt.

[33]  Y. Tohma,et al.  Circulating Levels of Orexin-A, Nesfatin-1, Agouti-Related Peptide, and Neuropeptide Y in Patients with Hyperthyroidism. , 2015, Thyroid : official journal of the American Thyroid Association.

[34]  S. Carr,et al.  Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior , 1998, Cell.

[35]  L. Lecea,et al.  Hypocretin (orexin) neuromodulation of stress and reward pathways , 2014, Current Opinion in Neurobiology.

[36]  P. Silveyra,et al.  Impact of proestrous milieu on expression of orexin receptors and prepro-orexin in rat hypothalamus and hypophysis: actions of Cetrorelix and Nembutal. , 2007, American journal of physiology. Endocrinology and metabolism.

[37]  M. Carotenuto,et al.  Executive dysfunction in children affected by obstructive sleep apnea syndrome: an observational study , 2013, Neuropsychiatric disease and treatment.

[38]  S. Chieffi,et al.  Age-related differences in distractor interference on line bisection , 2014, Experimental Brain Research.

[39]  Giovanni Messina,et al.  Orexin-A controls sympathetic activity and eating behavior , 2014, Front. Psychol..

[40]  S. Chieffi,et al.  Role of Orexin in Obese Patients in the Intensive Care Unit , 2014 .

[41]  H. Pijl,et al.  Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men. , 2005, American journal of physiology. Endocrinology and metabolism.

[42]  E. Wierzchoś,et al.  The role of orexin A in the control of prolactin and growth hormone secretions in sheep--in vitro study. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[43]  W. McNicholas,et al.  CrossTalk proposal: Metabolic syndrome causes sleep apnoea , 2016, The Journal of physiology.

[44]  Nancie J. MacIver,et al.  Increased leptin levels correlate with thyroid autoantibodies in nonobese males , 2016, Clinical endocrinology.

[45]  E. Bixler,et al.  Sleep apnea is a manifestation of the metabolic syndrome. , 2005, Sleep medicine reviews.

[46]  E. Mignot,et al.  High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy. , 2013, Sleep.

[47]  C. Jung,et al.  Serum Concentrations of Ghrelin and Leptin according to Thyroid Hormone Condition, and Their Correlations with Insulin Resistance , 2015, Endocrinology and metabolism.

[48]  F. Casanueva,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Cellular Localization of Orexin Receptors in , 2000 .

[49]  A. Alkemade.  Thyroid hormone and the developing hypothalamus , 2015, Front. Neuroanat..

[50]  T. Sakurai,et al.  Hypocretin/Orexin Neurons Contribute to Hippocampus-Dependent Social Memory and Synaptic Plasticity in Mice , 2013, The Journal of Neuroscience.

[51]  H. Haas,et al.  Orexin/Hypocretin Excites the Histaminergic Neurons of the Tuberomammillary Nucleus , 2001, The Journal of Neuroscience.

[52]  V. Luca,et al.  Quetiapine lowers sympathetic and hyperthermic reactions due to cerebral injection of orexin A , 2006, Neuropeptides.

[53]  Xuan Zhao,et al.  Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis , 2014, Peptides.

[54]  J. Szmyd,et al.  Experimental healing of preexisting gastric ulcers induced by hormones controlling food intake ghrelin, orexin-A and nesfatin-1 is impaired under diabetic conditions. A key to understanding the diabetic gastropathy? , 2013, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[55]  J. Renger,et al.  International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology , 2012, Pharmacological Reviews.

[56]  Edilio Borroni,et al.  Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice , 2011, Proceedings of the National Academy of Sciences.

[57]  D. Sikder,et al.  Feeding the heat on brown fat , 2013, Annals of the New York Academy of Sciences.

[58]  T. Yamamoto,et al.  Orexin-B-like immunoreactivity localized in both luteinizing hormone- and thyroid-stimulating hormone-containing cells in the Nile tilapia (Oreochromis niloticus) pituitary. , 2009, Tissue & cell.

[59]  G. Aston-Jones,et al.  Role of orexin input in the diurnal rhythm of locus coeruleus impulse activity , 2008, Brain Research.

[60]  S. Bloom,et al.  The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. , 2000, The Journal of clinical investigation.

[61]  P. Franco,et al.  High bicarbonate levels in narcoleptic children , 2016, Journal of sleep research.

[62]  E. Moura,et al.  [Regulation of thyrotropin synthesis and secretion]. , 2004, Arquivos brasileiros de endocrinologia e metabologia.

[63]  S. Corbett,et al.  Relationship of thyroid hormones and norepinephrine to the lateral hypothalamic syndrome. , 1986, Metabolism: clinical and experimental.

[64]  M. Dratman,et al.  Thyroid hormones as neurotransmitters. , 1996, Thyroid : official journal of the American Thyroid Association.

[65]  E. Mignot,et al.  Effects of Thyrotropin-Releasing Hormone and Its Analogs on Daytime Sleepiness and Cataplexy in Canine Narcolepsy , 1997, The Journal of Neuroscience.

[66]  J. Sweatt,et al.  A role for ERK MAP kinase in physiologic temporal integration in hippocampal area CA1. , 2003, Learning & memory.

[67]  F E Bloom,et al.  The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[68]  C. La Rocca,et al.  Serum levels of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in a population living in the Naples area, southern Italy. , 2014, Chemosphere.

[69]  T. Hanawa,et al.  I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation , 2008, Neuroscience.

[70]  V. Luca,et al.  Cortical spreading depression blocks the hyperthermic reaction induced by orexin a , 2004, Neuroscience.

[71]  C. Berridge,et al.  Hypocretin/orexin in arousal and stress , 2010, Brain Research.

[72]  F. Gage,et al.  Adult-Born Hippocampal Dentate Granule Cells Undergoing Maturation Modulate Learning and Memory in the Brain , 2009, The Journal of Neuroscience.

[73]  A. Nuñez,et al.  Synaptic interactions between perifornical lateral hypothalamic area, locus coeruleus nucleus and the oral pontine reticular nucleus are implicated in the stage succession during sleep-wakefulness cycle , 2013, Front. Neurosci..

[74]  G. Telegdy,et al.  The action of orexin A on passive avoidance learning. Involvement of transmitters , 2002, Regulatory Peptides.

[75]  Maria Rosaria Barillari,et al.  Role of orexin system in obesity , 2015 .

[76]  C. Small,et al.  Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter thyroid axis or uncoupling protein-1 in brown adipose tissue , 2002, Regulatory Peptides.

[77]  M. Tena-Sempere,et al.  Cross-talk between orexins (hypocretins) and the neuroendocrine axes (hypothalamic–pituitary axes) , 2010, Frontiers in Neuroendocrinology.

[78]  T. Nogimori,et al.  Effects of orexin A on thyrotropin-releasing hormone and thyrotropin secretion in rats. , 1999, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[79]  O. Basoglu,et al.  Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome , 2011, Annals of thoracic medicine.

[80]  M. Rotondi,et al.  Maternal hypothyroidism and subsequent neuropsychological outcome of the progeny: a family portrait , 2015, Endocrine.

[81]  A. N. van den Pol,et al.  Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems , 1998, The Journal of Neuroscience.

[82]  T. Sakurai,et al.  Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[83]  Larry R Squire,et al.  Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. , 2009, Learning & memory.

[84]  L. Capranica,et al.  Heart-Rate Changes After an Ultraendurance Swim From Italy to Albania: A Case Report. , 2016, International journal of sports physiology and performance.

[85]  M. G. Dube,et al.  Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action 1 This study was presented in part at the 28th Annual Meeting of the Society for Neuroscience, Los Angeles, CA, in November 1998. 1 , 1999, Brain Research.

[86]  C. Small,et al.  Central Administration of Orexin A Suppresses Basal and Domperidone Stimulated Plasma Prolactin , 2000, Journal of neuroendocrinology.

[87]  C. K. Song,et al.  Sympathetic and sensory innervation of brown adipose tissue , 2010, International Journal of Obesity.

[88]  J. Hagan,et al.  Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity , 2000, Psychopharmacology.

[89]  T. Yamamoto,et al.  Differential distribution of orexin-A-like and orexin receptor 1 (OX1R)-like immunoreactivities in the Xenopus pituitary. , 2007, Tissue & cell.

[90]  M. Nakazato,et al.  Centrally administered orexin/hypocretin activates HPA axis in rats , 2000, Neuroreport.

[91]  A. Wójtowicz,et al.  Effects of orexigenic peptides and leptin on melatonin secretion during different photoperiods in seasonal breeding ewes: an in vitro study. , 2011, Domestic animal endocrinology.

[92]  D. Cardinali,et al.  Ghrelin and its interactions with growth hormone, leptin and orexins: implications for the sleep-wake cycle and metabolism. , 2014, Sleep medicine reviews.

[93]  A. Viggiano,et al.  Mastication overload causes an increase in O2 − production into the subnucleus oralis of the spinal trigeminal nucleus , 2010, Neuroscience.

[94]  A. Kelley,et al.  Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action , 2001, Neuroscience.

[95]  A. Viggiano,et al.  Fast and low-cost analysis of heart rate variability reveals vegetative alterations in noncomplicated diabetic patients. , 2009, Journal of diabetes and its complications.

[96]  V. Luca,et al.  Olanzapine blocks the sympathetic and hyperthermic reactions due to cerebral injection of orexin A , 2008, Peptides.

[97]  E. Benarroch,et al.  Orexin/hypocretin system and autonomic control , 2014, Neurology.

[98]  TohmaYusuf,et al.  Circulating Levels of Orexin-A, Nesfatin-1, Agouti-Related Peptide, and Neuropeptide Y in Patients with Hyperthyroidism. , 2015 .

[99]  S. Schmid,et al.  The Sleep/Wake Cycle is Directly Modulated by Changes in Energy Balance. , 2016, Sleep.

[100]  M. Fernández-arquero,et al.  Narcolepsy with cataplexy and comorbid immunopathological diseases , 2014, Journal of sleep research.

[101]  J. Moon.  Endocrine Risk Factors for Cognitive Impairment , 2016, Endocrinology and metabolism.

[102]  D. Steindler,et al.  Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans. , 2010, Brain : a journal of neurology.

[103]  Giuseppe Cibelli,et al.  The Beneficial Effects of Coffee in Human Nutrition , 2015 .

[104]  M. Nakazato,et al.  Distribution of orexin/hypocretin in the rat median eminence and pituitary. , 2000, Brain research. Molecular brain research.

[105]  U. Galderisi,et al.  Sera of overweight people promote in vitro adipocyte differentiation of bone marrow stromal cells , 2014, Stem Cell Research & Therapy.

[106]  Giovanni Messina,et al.  Short-Term Diet and Moderate Exercise in Young Overweight Men Modulate Cardiocyte and Hepatocarcinoma Survival by Oxidative Stress , 2014, Oxidative medicine and cellular longevity.

[107]  S. Cortese,et al.  Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep , 2016, Acta paediatrica.

[108]  Takeshi Sakurai,et al.  Distribution of orexin neurons in the adult rat brain 1 Published on the World Wide Web on 17 March 1999. 1 , 1999, Brain Research.

[109]  V. Hubbard,et al.  Associations between adiposity and indicators of thyroid status in children and adolescents , 2016, Pediatric obesity.

[110]  M. Carotenuto,et al.  Depressive symptoms and childhood sleep apnea syndrome , 2012, Neuropsychiatric disease and treatment.

[111]  M. Serafin,et al.  Orexins (hypocretins) directly excite tuberomammillary neurons , 2001, The European journal of neuroscience.

[112]  K. Herzig,et al.  Functions of orexins in peripheral tissues , 2008, Acta physiologica.

[113]  W. Banks,et al.  Effects of orexin-A on memory processing , 2002, Peptides.

[114]  Takeshi Sakurai,et al.  Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System , 2009, Pharmacological Reviews.

[115]  J. Levine,et al.  Daily Intraparaventricular Orexin‐A Treatment Induces Weight Loss in Rats , 2009, Obesity.