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The N-Terminal Neurotensin Fragment, NT1–11, Inhibits Cortisol Secretion by Human Adrenocortical Cells

Institut National de la Santé et de la Recherche Médicale U 413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23) (F.S., V.C., H.L., D.A.-A., M.G., D.C., A.D., N.C., Y.A., H.V., C.D.), University of Rouen, 76821 Mont-Saint-Aignan, France; and Department of Endocrinology and Metabolic Diseases (H.L.), Centre Hospitalier Universitaire of Rouen, 76031 Rouen, France

Address all correspondence and requests for reprints to: Dr. Catherine Delarue, European Institute for Peptide Research (Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23), Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale U 413, University of Rouen, 76821 Mont-Saint-Aignan, France. E-mail: catherine.delarue{at}univ-rouen.fr.

Context: 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.

Design: In vitro studies were conducted on cultured human adrenocortical cells.

Setting: This study was conducted in a university research laboratory.

Patients: Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied.

Main Outcome Measure: 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.

Conclusion: 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.