Regulation of Aldosterone Secretion by Several Aberrant Receptors Including for Glucose-Dependent Insulinotropic Peptide in a Patient with an Aldosteronoma

Objective: The mechanisms inducing steroidogenesis in primary aldosteronism (PA) remain poorly defined. It was recently demonstrated that some G-protein-coupled receptors are abnormally expressed in aldosterone-producing adenomas (APA). We evaluated the potential role of LH and GNRH receptors (LHR (or LHCGR) and GNRHR) in regulating aldosterone secretion in a patient with APA arising during pregnancy (index case) and in a subset of other patients with PA. Patients and methods: GNRH test was performed in the index case, 11 other PA, and 5 controls. GNRHR and LHR expressions were examined in 23 APA and 6 normal tissues. Results: Aldosterone response increased significantly (114%) in the index case after GNRH test was performed preoperatively, while it was blunted after adrenalectomy. Aldosterone also increased after human chorionic gonadotropin and triptorelin stimulation. A partial aldosterone response to GNRH was observed in other 7/11 PA, while a significant response was observed in two patients. Controls did not respond to GNRH test. GNRHR was overexpressed and LHR expression was moderate in the APA tissue from the index case. Moreover, LHR was found in normal adrenals and overexpressed in 6/22 APA. GNRHR was overexpressed in 6/22 APA, 2 of them with a 95-and 109-fold higher expression than normal. A correlation between the clinical and molecular findings was observed in five out of seven patients. Conclusion: We describe a case of PA diagnosed during pregnancy, which appeared to correlate with aberrant LHR and GNRHR expression. Our findings suggest that a subset of patients with PA has aberrant LHR and GNRHR expression, which could modulate aldosterone secretion.

Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

Albiger¹,

Sartorato²,

Mariniello³

et al. 2011

“…Aldosterone secretion was stimulated by GIP in primary cultures of this patient's aldosteronoma. Real-time RT-PCR and immunohistochemistry found increased expression of GIPR as well as 5-HT 4 R and MC2R were also present (116,117). In a patient with BMAH and b-AR-aberrant expression, isoproterenol stimulated both cortisol and aldosterone production (117).…”

Section: Aberant Gpcr Is Not a Unique Feature Of Zona Fasciculata Cellsmentioning

confidence: 94%

“…Using a microarray approach in ten aldosteronomas compared with five normal adrenals and 13 cortisol-secreting adenomas, the six GCPRs with the highest increase in expression included LHCGR, 5-HT 4 R, GnRHR, glutamate receptor metabotropic three, endothelin receptor ET B receptors and MC2R (101). Renin-independent stimulation of aldosterone secretion was observed in vivo following mixed meal, oral glucose, or administration of GIP, vasopressin and tegaserod in a patient with unilateral source of PA (116). Aldosterone secretion was stimulated by GIP in primary cultures of this patient's aldosteronoma.…”

Section: Aberant Gpcr Is Not a Unique Feature Of Zona Fasciculata Cellsmentioning

confidence: 99%

Multiple aberrant hormone receptors in Cushing's syndrome

Ghorayeb

Bourdeau

Lacroix

2015

Self Cite

“…Besides the increase in potential intra-adrenal sources of 5-HT, other defects favoring the stimulatory action of 5-HT on steroidogenic cells have been described in adrenocortical neoplasms. In particular, patients with aldosteronoma exhibit exaggerated plasma aldosterone responses to the 5-HT 4 receptor agonists metoclopramide (131,156) and tegaserod (157). This increased responsiveness of aldosterone-producing adenomas to serotonergic agents can be ascribed to overexpression of 5-HT 4 receptor mRNAs, which has been well documented in aldosteronoma tissues in comparison with normal adrenals (71,131,158,159).…”

Section: Factorsmentioning

confidence: 98%

MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

Lefebvre

Prévost

Louiset

2013

A wide variety of autocrine/paracrine bioactive signals are able to modulate corticosteroid secretion in the human adrenal gland. These regulatory factors, released in the vicinity of adrenocortical cells by diverse cell types comprising chromaffin cells, nerve terminals, cells of the immune system, endothelial cells, and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.European Journal of Endocrinology 169 R115-R138