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Journal articles

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

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.
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Contributor : Céline Duparc Connect in order to contact the contributor
Submitted on : Tuesday, November 20, 2018 - 5:44:03 PM
Last modification on : Wednesday, March 2, 2022 - 3:48:01 PM


  • HAL Id : hal-01928812, version 1
  • PUBMED : 15666851


Estelle Louiset, Dorthe Cartier, Vincent Contesse, Céline Duparc, Isabelle Lihrmann, et al.. Paradoxical inhibitory effect of serotonin on cortisol production from adrenocortical lesions causing Cushing's syndrome.. Endocrine Research, Taylor & Francis, 2004, pp.951-4. ⟨hal-01928812⟩



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