title: The human endolymphatic sac expresses natriuretic peptides.
abstract: The function of the human endolymphatic sac (ES) has been enigmatic for decades. Hypotheses include controlling endolymphatic fluid homeostasis and inner ear immunological defense. Additionally, several studies indicate a possible endocrine capacity and a yet undefined role in intracranial pressure homeostasis. However, no direct evidence of such capacity exists. This study aims to explore and identify the hypothesized endocrine capacity of the human ES.
  
  
  
  DNA microarrays and immunohistochemistry were used for analyses of fresh human ES tissue samples.
  
  
  
  Twelve tissue samples from the human ES were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample gene expression. Genes specific for an endocrine function were determined, and results were verified by immunohistochemistry.
  
  
  
  Several natriuretic peptides were found expressed significantly in the ES, including uroguanylin and brain natriuretic peptide, but also peptides regulating vascular tone, including adrenomedullin 2. In addition, both neurophysin and oxytocin (OXT) were found significantly expressed. All peptides were verified by immunohistochemistry.
  
  
  
  The present data support the hypothesis that the human ES may have an endocrine/paracrine capacity through expression of several peptides with potent natriuretic activity. Furthermore, the ES may influence the hypothalamo-pituitary-adrenal axis and may regulate vasopressin receptors and aquaporin-2 channels in the inner ear via OXT expression. We hypothesize that the ES is likely to regulate inner ear endolymphatic homeostasis, possibly through secretion of several peptides, but it may also influence systemic and/or intracranial blood pressure through direct and indirect action on the vascular system and the kidney.
  
  
  
  NA. Laryngoscope, 127:E201-E208, 2017.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Martin Nue
authors.initials: MN
authors.lastname: Møller
authors.affiliation: Department of Oral Medicine, Dental School, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Svend
authors.initials: S
authors.lastname: Kirkeby
authors.affiliation: Center for Genomic Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Vikeså
authors.affiliation: Center for Genomic Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Rigshospitalet, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Cayé-Thomasen
mesh_terms: D007758:Ear, Inner / Q000601:surgery; D004710:Endolymph / Q000378:metabolism*; D004712:Endolymphatic Sac / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D045265:Natriuretic Peptides / Q000378:metabolism*; D009464:Neuroma, Acoustic / Q000473:pathology / Q000601:surgery; D009481:Neurophysins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010121:Oxytocin / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism
chemical_list: C484330:ADM2 protein, human; D045265:Natriuretic Peptides; D009481:Neurophysins; D036361:Peptide Hormones; D020097:Natriuretic Peptide, Brain; C084362:uroguanylin; D010121:Oxytocin
keywords: Endolymphatic sac; Meniere; inner ear; microarray; natriuretic peptide