The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.
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.
Sicard
Flavie
F
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.
Contesse
Vincent
V
Lefebvre
Hervé
H
Ait-Ali
Djida
D
Gras
Marjorie
M
Cartier
Dorthe
D
Decker
Annick
A
Chartrel
Nicolas
N
Anouar
Youssef
Y
Vaudry
Hubert
H
Delarue
Catherine
C
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
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)