Expression of serotonin7 receptor and coupling of ectopic receptors to protein kinase A and ionic currents in adrenocorticotropin-independent macronodular adrenal hyperplasia causing Cushing's syndrome.

Abstract

CONTEXT:

In ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing's syndrome, cortisol secretion is controlled by illegitimate membrane receptors.

OBJECTIVE:

The aim of the present study was to characterize the pharmacological properties and the transduction mechanisms of illegitimate receptors, i.e. receptors for serotonin (5-HT), gastric inhibitory polypeptide (GIP), and LH/human chorionic gonadotropin (hCG), expressed by AIMAH tissues to evaluate the role of ectopic receptors in the physiopathology of Cushing's syndrome.

DESIGN:

We used in vitro studies on cultured adrenal hyperplasia cells.

SETTING:

The setting was a university research laboratory.

PATIENTS:

AIMAH tissues (H1-H3) were removed from three patients previously screened for illegitimate receptors.

MAIN OUTCOME MEASURE(S):

The main outcome measures were steroidogenic and electrical activities of cultured adrenal hyperplasia cells.

RESULTS:

In vitro studies showed that the corticotropic effect of 5-HT was mediated by ectopic 5-HT7 receptors in H1 and H2. GIP and hCG stimulated cortisol production via activation of cAMP-dependent protein kinase A in H2. On the contrary, the protein kinase A inhibitor H-89 did not affect hCG-induced cortisol production in H3. Activation of 5-HT7 or GIP receptors enhanced T-type calcium current in H1 or H2 and H3, respectively. In addition, GIP reduced the amplitude of transient and sustained potassium currents in H2. Conversely, hCG did not modify T-type calcium current in H3.

CONCLUSIONS:

These data show that, besides their coupling to the cAMP pathway, illegitimate adrenal receptors can activate additional transduction mechanisms, including modulation of membrane channels.

• Authors: Estelle Louiset, Vincent Contesse, Lionel Groussin, Dorthe Cartier, Céline Duparc, Gaëlle Barrande, Jérôme Bertherat, Hubert Vaudry, Hervé Lefebvre
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 91 Issue 11 Pg. 4578-86 (Nov 2006) ISSN: 0021-972X [Print] United States
• PMID: 16954157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ion Channels
• Receptors, Gastrointestinal Hormone
• Receptors, LH
• Receptors, Serotonin
• serotonin 7 receptor
• Adrenocorticotropic Hormone
• gastric inhibitory polypeptide receptor
• Cyclic AMP-Dependent Protein Kinases
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (metabolism)
• Adrenal Glands (metabolism, pathology)
• Adrenocorticotropic Hormone (metabolism)
• Adult
• Cells, Cultured
• Cushing Syndrome (etiology, metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism, physiology)
• Female
• Gene Expression
• Humans
• Hyperplasia
• In Vitro Techniques
• Ion Channels (metabolism)
• Middle Aged
• Receptors, Gastrointestinal Hormone (metabolism)
• Receptors, LH (metabolism)
• Receptors, Serotonin (metabolism, physiology)
• Signal Transduction (physiology)