title: The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.
abstract: BACKGROUND
  Neurotensin (NT) modulates corticosteroid secretion from the mammalian adrenal gland.
  
  
  OBJECTIVE
  The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland.
  
  
  METHODS
  In vitro studies were conducted on cultured human adrenocortical cells.
  
  
  METHODS
  This study was conducted in a university research laboratory.
  
  
  METHODS
  Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied.
  
  
  METHODS
  Cortisol secretion from cultured adrenocortical cells was measured.
  
  
  RESULTS
  NT1-11, the N-terminal fragment of NT, dose-dependently inhibited basal and ACTH-stimulated cortisol production by human adrenocortical cells in primary culture. In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m. HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts. Molecular and pharmacological studies were performed to determine the type of NT receptor involved in the corticostatic effect of NT1-11. RT-PCR analysis revealed the expression of NT receptor type (NTR) 3 mRNA but not NTR1 and NTR2 mRNAs in the human adrenal tissue. However, the pharmacological profile of the adrenal NT1-11 receptor was different from that of NTR3, indicating that this receptor type is not involved in the action of NT1-11 on corticosteroidogenesis.
  
  
  CONCLUSIONS
  Our results indicate that NT1-11 may act as an endocrine factor to inhibit cortisol secretion through activation of a receptor distinct from the classical NTR1, NTR2, and NTR3.
authors.affiliation: INSERM Unité 413, European Institute for Peptide Research (Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23), Laboratory of Cellular and Molecular Neuroendocrinology, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Sicard
authors.forename: Vincent
authors.initials: V
authors.lastname: Contesse
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefebvre
authors.forename: Djida
authors.initials: D
authors.lastname: Ait-Ali
authors.forename: Marjorie
authors.initials: M
authors.lastname: Gras
authors.forename: Dorthe
authors.initials: D
authors.lastname: Cartier
authors.forename: Annick
authors.initials: A
authors.lastname: Decker
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Catherine
authors.initials: C
authors.lastname: Delarue
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000302:Adrenal Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009496:Neurotensin / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D018028:Receptors, Neurotensin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009496:Neurotensin; D010446:Peptide Fragments; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; D000099183:Sortilin; C059582:neurotensin (1-11)