title: Catecholaminergic axonal varicosities appear to innervate growth hormone-releasing hormone-immunoreactive neurons in the human hypothalamus: the possible morphological substrate of the stress-suppressed growth.
abstract: BACKGROUND
  Stress is considered to be a major factor in the regulation of growth. Psychosocial dwarfism, characterized with short stature, delayed puberty, and depression, is typically preceded by psychological harassment or stressful environment. It has been observed that stress suppresses GH secretion, possibly via the attenuation of GHRH secretion. However, the exact mechanism of the impact of stress on growth has not been elucidated yet.
  
  
  OBJECTIVE
  Our previous studies revealed intimate associations between neuropeptide Y (NPY)-immunoreactive (IR) axonal varicosities and GHRH-IR perikarya in the human hypothalamus. Because NPY is considered to be a stress molecule, NPY-GHRH juxtapositions may represent an important factor of stress-suppressed GHRH release. In addition to NPY, catecholamines are among the major markers of stress. Thus, in the present study, we examined the putative juxtapositions between the catecholaminergic tyrosine hydroxylase (TH)-/dopamine-β-hydroxylase-/phenylethanolamine N-methyltransferase-IR and GHRH-IR neural elements in the human hypothalamus. To reveal these juxtapositions, double-label immunohistochemistry was used.
  
  
  RESULTS
  Our findings revealed that the majority of the GHRH-IR perikarya formed intimate associations with TH-IR fiber varicosities. The majority of these juxtapositions were found in the infundibular nucleus/median eminence.
  
  
  CONCLUSIONS
  The lack of phenylethanolamine N-methyltransferase-GHRH associations and the small number of dopamine-β-hydroxylase-GHRH juxtapositions suggest that the vast majority of the observed TH-GHRH juxtapositions represent dopaminergic associations. The density of the abutting TH-IR fibers on the surface of the GHRH perikarya suggests that these juxtapositions may be functional synapses, and thus, in addition to NPY, catecholamines may regulate GHRH secretion via direct synaptic mechanisms.
authors.affiliation: Neuroendocrine Organization Laboratory, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Boulevard, Erie, Pennsylvania 16509, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Rotoli
authors.forename: George
authors.initials: G
authors.lastname: Grignol
authors.forename: Walter
authors.initials: W
authors.lastname: Hu
authors.forename: Istvan
authors.initials: I
authors.lastname: Merchenthaler
authors.forename: Bertalan
authors.initials: B
authors.lastname: Dudas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001369:Axons / Q000473:pathology* / Q000502:physiology; D001931:Brain Mapping; D002395:Catecholamines / Q000502:physiology*; D004027:Diencephalon / Q000473:pathology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005260:Female; D006130:Growth Disorders / Q000209:etiology* / Q000473:pathology*; D013007:Growth Hormone-Releasing Hormone / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000473:pathology* / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D013315:Stress, Psychological / Q000473:pathology*; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002395:Catecholamines; D013007:Growth Hormone-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase