Paradoxical inhibitory effect of serotonin on cortisol production from adrenocortical lesions causing Cushing's syndrome.

Estelle Louiset; Dorthe Cartier; Vincent Contesse; Céline Duparc; Isabelle Lihrmann; J Young; Jérôme Bertherat; Y. Reznik; Jean-Marc Kuhn; A. Laquerriere; H. Vaudry; Hervé Lefebvre

Journal articles

Paradoxical inhibitory effect of serotonin on cortisol production from adrenocortical lesions causing Cushing's syndrome.

Estelle Louiset ^{1, 2} Dorthe Cartier ^{1, 2} Vincent Contesse ³ Céline Duparc ^{1, 2} Isabelle Lihrmann ^{1, 2} J Young Jérôme Bertherat ^{4, 5, 6, 7, 8} Y. Reznik ⁹ Jean-Marc Kuhn ^{3, 10} A. Laquerriere ¹¹ H. Vaudry ² Hervé Lefebvre ^{1, 2, 10}

1 DC2N - Différenciation et communication neuronale et neuroendocrine

2 DC2N - Différenciation et communication neuronale et neuroendocrine

3 Neuroendocrinologie cellulaire et moléculaire

4 UMR_S567 / UMR 8104 - Institut Cochin

5 EMD - [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD)

6 CHU Cochin [AP-HP]

7 IFRAJ - Institut Fédératif de Recherche Alfred Jost

8 UPD5 - Université Paris Descartes - Paris 5

9 Service d'endocrinologie [CHU Caen]

10 Service d'endocrinologie, diabétologie et maladies métaboliques [Rouen]

11 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]

Abstract : In the human adrenal gland, serotonin (5-HT) stimulates cortisol production through a paracrine mechanism involving 5-HT4 receptors positively-coupled to adenylyl cyclase. A hyperresponsiveness of adrenocortical tissue to 5-HT has also been described in several cases of ACTH-independent bilateral macronodular adrenal hyperplasias (AIMAHs) and adenomas causing Cushing's syndrome. In the present study, we report two cases of cortisol-producing adrenocortical lesions, i.e., one AIMAH (case 1) and one adenoma (case 2), whose secretory activity was inhibited in vitro by 5-HT. The potencies (pIC50) and efficacies (Emax) of 5-HT to inhibit cortisol secretion were 8.2 +/- 0.4 and -64.1% +/- 7.5% in case 1, and 9.2 +/- 0.5 and -32.3% +/- 3.8% in case 2. The specific 5-HT4 antagonist GR 113808 failed to influence the 5-HT-induced decrease in cortisol production by the two tissues, indicating that the paradoxical inhibitory effect of 5-HT could not be accounted for by activation of eutopic 5-HT4 receptors. These results suggest that the tissues expressed aberrant 5-HT receptors. In conclusion, the present study provides the first evidence for an inhibitory effect of 5-HT on cortisol secretion in adrenocortical lesions causing Cushing's syndrome. Our data also suggest that expression of illegitimate membrane receptors by cortisol-producing adrenal hyperplasias and/or adenomas may convert a paracrine stimulatory factor into an inhibitory signal.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Human health and pathology / Endocrinology and metabolism

Complete list of metadatas

https://hal-normandie-univ.archives-ouvertes.fr/hal-01928812
Contributor : Céline Duparc <>
Submitted on : Tuesday, November 20, 2018 - 5:44:03 PM
Last modification on : Wednesday, May 6, 2020 - 1:30:36 AM

Paradoxical inhibitory effect of serotonin on cortisol production from adrenocortical lesions causing Cushing's syndrome.

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Paradoxical inhibitory effect of serotonin on cortisol production from adrenocortical lesions causing Cushing's syndrome.

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