Advertisement

Cell and Tissue Research

, Volume 368, Issue 1, pp 115–123 | Cite as

Identification of an endocannabinoid system in the rat pars tuberalis—a possible interface in the hypothalamic-pituitary-adrenal system?

  • Arsalan Jafarpour
  • Faramarz Dehghani
  • Horst-Werner KorfEmail author
Regular Article

Abstract

Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research. By means of immunocytochemistry, enzymes involved in EC biosynthesis, e.g., N-arachidonoyl-phosphatidylethanolamine-phospholipase D (NAPE-PLD) and diacylglycerol lipase α (DAGLα) and enzymes involved in EC degradation, e.g., fatty acid amide hydrolase (FAAH) and cyclooxygenase-2 (COX-2), were demonstrated in PT cells of the rat. Immunoreactions (IR) for FAAH and for the cannabinoid receptor CB1 were observed in corticotrope cells of the rat adenohypophysis; these cells were identified by antibodies against proopiomelanocortin (POMC) or adrenocorticotrophic hormone (ACTH). In the outer zone of the median eminence, numerous nerve fibers and terminals displayed CB1 IR. The majority of these were also immunolabeled by an antibody against corticotropin-releasing factor (CRF). These results suggest that the EC system at the hypothalamo-hypophysial interface affects both the CRF-containing nerve fibers and the corticotrope cells in the adenohypophysis. Our data give rise to the hypothesis that, in addition to its well-known role in the reproductive axis, the PT might influence adrenal functions and, thus, the stress response and immune system.

Keywords

Endocannabinoid system Pars tuberalis Cannabinoid receptor Hypothalamic-pituitary-adrenal axis Corticotropin-releasing factor 

References

  1. Alexander SP, Kendall DA (2007) The complications of promiscuity: endocannabinoid action and metabolism. Br J Pharmacol 152:602–623CrossRefPubMedPubMedCentralGoogle Scholar
  2. Astarita G, Ahmed F, Piomelli D (2008) Identification of biosynthetic precursors for the endocannabinoid anandamide in the rat brain. J Lipid Res 49:48–57CrossRefPubMedGoogle Scholar
  3. Cachope R (2012) Functional diversity on synaptic plasticity mediated by endocannabinoids. Philos Trans R Soc Lond Ser B Biol Sci 367:3242–3253CrossRefGoogle Scholar
  4. Cota D, Steiner MA, Marsicano G, Cervino C, Herman JP, Grubler Y, Stalla J, Pasquali R, Lutz B, Stalla GK, Pagotto U (2007) Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology 148:1574–1581CrossRefPubMedGoogle Scholar
  5. Cristino L, Petrocellis L de, Pryce G, Baker D, Guglielmotti V, Di Marzo V (2006) Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience 139:1405–1415Google Scholar
  6. Cristino L, Becker T, Di Marzo V (2014) Endocannabinoids and energy homeostasis: an update. Biofactors 40:389–397CrossRefPubMedGoogle Scholar
  7. Crosby KM, Bains JS (2011) The intricate link between glucocorticoids and endocannabinoids at stress-relevant synapses in the hypothalamus. Neuroscience 204:31–37CrossRefPubMedGoogle Scholar
  8. Crowe MS, Nass SR, Gabella KM, Kinsey SG (2014) The endocannabinoid system modulates stress, emotionality, and inflammation. Brain Behav Immun 42:1–5CrossRefPubMedGoogle Scholar
  9. Dardente H (2012) Melatonin-dependent timing of seasonal reproduction by the pars tuberalis: pivotal roles for long daylengths and thyroid hormones. J Neuroendocrinol 24:249–266CrossRefPubMedGoogle Scholar
  10. Dardente H, Hazlerigg DG, Ebling FJ (2014) Thyroid hormone and seasonal rhythmicity. Front Endocrinol 5:19CrossRefGoogle Scholar
  11. Dardente H, Lomet D, Robert V, Decourt C, Beltramo M, Pellicer-Rubio MT (2016) Seasonal breeding in mammals: from basic science to applications and back. Theriogenology 86:324–332CrossRefPubMedGoogle Scholar
  12. De Laurentiis A, Araujo HA, Rettori V (2014) Role of the endocannabinoid system in the neuroendocrine responses to inflammation. Curr Pharm Des 20:4697–4706CrossRefPubMedGoogle Scholar
  13. Dickens MJ, Vecchiarelli HA, Hill MN, Bentley GE (2015) Endocannabinoid signaling in the stress response of male and female songbirds. Endocrinology 156:4649–4659CrossRefPubMedPubMedCentralGoogle Scholar
  14. Dupré SM, Miedzinska K, Duval CV, Yu L, Goodman RL, Lincoln GA, Davis JR, McNeilly AS, Burt DD, Loudon AS (2010) Identification of Eya3 and TAC1 as longday signals in the sheep pituitary. Curr Biol 20:829–835CrossRefPubMedPubMedCentralGoogle Scholar
  15. Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience 119:481–496CrossRefPubMedGoogle Scholar
  16. Egertova M, Simon GM, Cravatt BF, Elphick MR (2008) Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: a new perspective on N-acylethanolamines as neural signaling molecules. J Comp Neurol 506:604–615CrossRefPubMedGoogle Scholar
  17. Ernst J, Grabiec U, Greither T, Fischer B, Dehghani F (2016) The endocannabinoid system in the human granulosa cell line KGN. Mol Cell Endocrinol 423:67–76CrossRefPubMedGoogle Scholar
  18. Ferreira SG, Teixeira FM, Garcao P, Agostinho P, Ledent C, Cortes L, Mackie K, Kofalvi A (2012) Presynaptic CB(1) cannabinoid receptors control frontocortical serotonin and glutamate release— species differences. Neurochem Int 61:219–226Google Scholar
  19. Fischer C, Christ E, Korf HW, Gall C von (2012) Tafa-3 encoding for a secretory peptide is expressed in the mouse pars tuberalis and is affected by melatonin 1 receptor deficiency. Gen Comp Endocrinol 177:98–103Google Scholar
  20. Fowler CJ (2007) The contribution of cyclooxygenase-2 to endocannabinoid metabolism and action. Br J Pharmacol 152:594–601CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gall C von, Garabette ML, Kell CA, Frenzel S, Dehghani F, Schumm-Draeger PM, Weaver DR, Korf HW, Hastings MH, Stehle JH (2002) Rhythmic gene expression in pituitary depends on heterologous sensitization by the neurohormone melatonin. Nat Neurosci 5:234–238Google Scholar
  22. Gulyas AI, Cravatt BF, Bracey MH, Dinh TP, Piomelli D, Boscia F, Freund TF (2004) Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 20:441–458CrossRefPubMedGoogle Scholar
  23. Hardeland R, Pandi-Perumal SR, Cardinali DP (2006) Melatonin. Int J Biochem Cell Biol 38:313–316CrossRefPubMedGoogle Scholar
  24. Hermann H, Lutz B (2005) Coexpression of the cannabinoid receptor type 1 with the corticotropin-releasing hormone receptor type 1 in distinct regions of the adult mouse forebrain. Neurosci Lett 375:13–18CrossRefPubMedGoogle Scholar
  25. Hill MN, McLaughlin RJ, Bingham B, Shrestha L, Lee TT, Gray JM, Hillard CJ, Gorzalka BB, Viau V (2010) Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci U S A 107:9406–9411CrossRefPubMedPubMedCentralGoogle Scholar
  26. Hillard CJ (2014) Stress regulates endocannabinoid-CB1 receptor signaling. Semin Immunol 26:380–388CrossRefPubMedPubMedCentralGoogle Scholar
  27. Ikegami K, Yoshimura T (2012) Circadian clocks and the measurement of daylength in seasonal reproduction. Mol Cell Endocrinol 349:76–81CrossRefPubMedGoogle Scholar
  28. Ikegami K, Yoshimura T (2016) Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction. Gen Comp Endocrinol 227:64–68CrossRefPubMedGoogle Scholar
  29. Ikegami K, Liao XH, Hoshino Y, Ono H, Ota W, Ito Y, Nishiwaki-Ohkawa T, Sato C, Kitajima K, Iigo M, Shigeyoshi Y, Yamada M, Murata Y, Refetoff S, Yoshimura T (2014) Tissue-specific posttranslational modification allows functional targeting of thyrotropin. Cell Rep 9:801–810CrossRefPubMedPubMedCentralGoogle Scholar
  30. Jourdan T, Godlewski G, Kunos G (2016) Endocannabinoid regulation of beta-cell functions: implications for glycaemic control and diabetes. Diabetes Obes Metab 18:549–557CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kallendrusch S, Hobusch C, Ehrlich A, Nowicki M, Ziebell S, Bechmann I, Geisslinger G, Koch M, Dehghani F (2012) Intrinsic up-regulation of 2-AG favors an area specific neuronal survival in different in vitro models of neuronal damage. PLoS ONE 7:e51208CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kalsbeek A, Spek R van der, Lei J, Endert E, Buijs RM, Fliers E (2012) Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis. Mol Cell Endocrinol 349:20–29Google Scholar
  33. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380CrossRefPubMedGoogle Scholar
  34. Katona I, Freund TF (2012) Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 35:529–558CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M (2006) The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 26:2991–3001CrossRefPubMedGoogle Scholar
  36. Koch M, Habazettl I, Dehghani F, Korf HW (2008) The rat pineal gland comprises an endocannabinoid system. J Pineal Res 45:351–360CrossRefPubMedGoogle Scholar
  37. Kolbe I, Dumbell R, Oster H (2015) Circadian clocks and the interaction between stress axis and adipose function. Int J Endocrinol 2015:693204CrossRefPubMedPubMedCentralGoogle Scholar
  38. Lu HC, Mackie K (2016) An introduction to the endogenous cannabinoid system. Biol Psychiatry 79:516–525CrossRefPubMedGoogle Scholar
  39. Manders EMM, Verbeek FJ, Aten JA (1993) Measurement of colocalization of objects in dual-color confocal images. J Microsc (Oxford) 169:375–382CrossRefGoogle Scholar
  40. Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, Stelt M van der, Lopez-Rodriguez ML, Casanova E, Schutz G, Zieglgansberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88Google Scholar
  41. Mayo JC, Sainz RM, Tan DX, Hardeland R, Leon J, Rodriguez C, Reiter RJ (2005) Anti-inflammatoryactions ofmelatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine(AMK), in macrophages. J Neuroimmunol 165:139–149CrossRefPubMedGoogle Scholar
  42. Mazier W, Saucisse N, Gatta-Cherifi B, Cota D (2015) The endocannabinoid system: pivotal orchestrator of obesity and metabolic disease. Trends Endocrinol Metab 26:524–537CrossRefPubMedGoogle Scholar
  43. Muccioli GG (2010) Endocannabinoid biosynthesis and inactivation, from simple to complex. Drug Discov Today 15:474–483CrossRefPubMedGoogle Scholar
  44. Nakao N, Ono H, Yamamura T, Anraku T, Takagi T, Higashi K, Yasuo S, Katou Y, Kageyama S, Uno Y, Kasukawa T, Iigo M, Sharp PJ, Iwasawa A, Suzuki Y, Sugano S, Niimi T, Mizutani M, Namikawa T, Ebihara S, Ueda HR, Yoshimura T (2008) Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature 452:317–322CrossRefPubMedGoogle Scholar
  45. Nishiwaki-Ohkawa T, Yoshimura T (2016) Molecular basis for regulating seasonal reproduction in vertebrates. J Endocrinol 229:R117–R127CrossRefPubMedGoogle Scholar
  46. Ohno-Shosaku T, Kano M (2014) Endocannabinoid-mediated retrograde modulation of synaptic transmission. Curr Opin Neurobiol 29:1–8CrossRefPubMedGoogle Scholar
  47. Ono H, Nakao N, Yoshimura T (2009) Identification of the photoperiodic signaling pathway regulating seasonal reproduction using the functional genomics approach. Gen Comp Endocrinol 163:2–6CrossRefPubMedGoogle Scholar
  48. Oropeza VC, Mackie K, Van Bockstaele EJ (2007) Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex. Brain Res 1127:36–44CrossRefPubMedGoogle Scholar
  49. Pagotto U, Marsicano G, Fezza F, Theodoropoulou M, Grubler Y, Stalla J, Arzberger T, Milone A, Losa M, Di Marzo V, Lutz B, Stalla GK (2001) Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level. J Clin Endocrinol Metab 86:2687–2696PubMedGoogle Scholar
  50. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R (2006) The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 27:73–100CrossRefPubMedGoogle Scholar
  51. Piomelli D (2003) The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 4:873–884CrossRefPubMedGoogle Scholar
  52. Reguero L, Puente N, Elezgarai I, Ramos-Uriarte A, Gerrikagoitia I, Bueno-Lopez JL, Donate F, Grandes P (2014) Subcellular localization of NAPE-PLD and DAGL-alpha in the ventromedial nucleus of the hypothalamus by a preembedding immunogold method. Histochem Cell Biol 141:543–550CrossRefPubMedGoogle Scholar
  53. Rivera P, Arrabal S, Vargas A, Blanco E, Serrano A, Pavon FJ, Rodriguez de Fonseca F, Suarez J (2014) Localization of peroxisome proliferator-activated receptor alpha (PPARα) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca2+−binding proteins calbindin, calretinin and parvalbumin in the adult rat hippocampus. Front Neuroanat 8:12PubMedPubMedCentralGoogle Scholar
  54. Ross AW, Morgan PJ (2002) The pars tuberalis as a target of the central clock. Cell Tissue Res 309:163–171CrossRefPubMedGoogle Scholar
  55. Saenz de Miera C, Monecke S, Bartzen-Sprauer J, Laran-Chich MP, Pevet P, Hazlerigg DG, Simonneaux V (2014) A circannual clock drives expression of genes central for seasonal reproduction. Curr Biol 24:1500–1506CrossRefPubMedGoogle Scholar
  56. Starowicz KM, Cristino L, Matias I, Capasso R, Racioppi A, Izzo AA, Di Marzo V (2008) Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet. Obesity (Silver Spring) 16:553–565CrossRefGoogle Scholar
  57. Stirland JA, Johnston JD, Cagampang FR, Morgan PJ, Castro MG, White MR, Davis JR, Loudon AS (2001) Photoperiodic regulation of prolactin gene expression in the Syrian hamster by a pars tuberalis-derived factor. J Neuroendocrinol 13:147–157CrossRefPubMedGoogle Scholar
  58. Uchigashima M, Narushima M, Fukaya M, Katona I, Kano M, Watanabe M (2007) Subcellular arrangement of molecules for 2-arachidonoyl-glycerol-mediated retrograde signaling and its physiological contribution to synaptic modulation in the striatum. J Neurosci 27:3663–3676CrossRefPubMedGoogle Scholar
  59. Viau V (2002) Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes. J Neuroendocrinol 14:506–13CrossRefPubMedGoogle Scholar
  60. Wittmann G, Deli L, Kallo I, Hrabovszky E, Watanabe M, Liposits Z, Fekete C (2007) Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus. J Comp Neurol 503:270–279CrossRefPubMedGoogle Scholar
  61. Wood SH, Christian HC, Miedzinska K, Saer BR, Johnson M, Paton B, Yu L, McNeilly J, Davis JR, McNeilly AS, Burt DW, Loudon AS (2015) Binary switching of calendar cells in the pituitary defines the phase of the circannual cycle in mammals. Curr Biol 25:2651–2662CrossRefPubMedPubMedCentralGoogle Scholar
  62. Yasuo S, Korf HW (2011) The hypophysial pars tuberalis transduces photoperiodic signals via multiple pathways and messenger molecules. Gen Comp Endocrinol 172:15–22CrossRefPubMedGoogle Scholar
  63. Yasuo S, Koch M, Schmidt H, Ziebell S, Bojunga J, Geisslinger G, Korf HW (2010a) An endocannabinoid system is localized to the hypophysial pars tuberalis of Syrian hamsters and responds to photoperiodic changes. Cell Tissue Res 340:127–136CrossRefPubMedGoogle Scholar
  64. Yasuo S, Unfried C, Kettner M, Geisslinger G, Korf HW (2010b) Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man. Cell Tissue Res 342:273–281CrossRefPubMedGoogle Scholar
  65. Yasuo S, Fischer C, Bojunga J, Iigo M, Korf HW (2014) 2-Arachidonoyl glycerol sensitizes the pars distalis and enhances forskolin-stimulated prolactin secretion in Syrian hamsters. Chronobiol Int 31:337–342CrossRefPubMedGoogle Scholar
  66. Yoshida T, Fukaya M, Uchigashima M, Miura E, Kamiya H, Kano M, Watanabe M (2006) Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J Neurosci 26:4740–4751CrossRefPubMedGoogle Scholar
  67. Yoshida T, Uchigashima M, Yamasaki M, Katona I, Yamazaki M, Sakimura K, KanoM YM, Watanabe M (2011) Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus. Proc Natl Acad Sci U S A 108:3059–3064CrossRefPubMedPubMedCentralGoogle Scholar
  68. Yoshimura T (2013) Thyroid hormone and seasonal regulation of reproduction. Front Neuroendocrinol 34:157–166CrossRefPubMedGoogle Scholar
  69. Zhang MZ, Harris RC, McKanna JA (1999) Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids. Proc Natl Acad Sci U S A 96:15280–15285CrossRefPubMedPubMedCentralGoogle Scholar
  70. Zheng G, Hong S, Hayes JM, Wiley JW (2015) Chronic stress and peripheral pain: evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways. Exp Neurol 273:301–311CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Arsalan Jafarpour
    • 1
    • 2
  • Faramarz Dehghani
    • 1
    • 3
  • Horst-Werner Korf
    • 1
    • 4
    Email author
  1. 1.Dr. Senckenbergische Anatomie, Institut der Anatomie IIJohann Wolfgang Goethe-UniversitätFrankfurt am MainGermany
  2. 2.Department für Neurologie, Klinik für Schlafmedizin und Neuromuskuläre ErkrankungenUniversitätsklinikum MünsterMünsterGermany
  3. 3.Institut für Anatomie und ZellbiologieMartin-Luther-Universität Halle-WittenbergHalle (Saale)Germany
  4. 4.Dr.Senckenbergisches Chronomedizinisches InstitutJohann Wolfgang Goethe-UniversitätFrankfurt MainGermany

Personalised recommendations