EMAIL THIS PAGE TO A FRIEND

Endocrinology

Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid in a cellular model of Cushing's disease mediates the inhibition of cell proliferation and ACTH secretion without a complete corticotroph-to-melanotroph transdifferentiation.


PMID 24926820

Abstract

Cushing's disease (CD) is a rare condition in which hypercortisolemia is secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is associated with significant morbidity and mortality, and a safe therapy that effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and dopamine agonists (DAs) have recently been considered as monotherapy in CD patients, and satisfactory results have been reported, albeit in a limited number of patients. Given the permissive role of RA on the dopamine receptor type-2 (DRD2), the aim of the present study was to see whether a combination of 9-cis RA and the DA bromocriptine (Br) might represent a possible treatment for CD. Here we show that 9-cis RA induces a functional DRD2 in the pituitary corticotroph cell line AtT20, and increases cell sensitivity to Br via a mechanism only partially related to corticotroph-to-melanotroph transdifferentiation. In addition, 9-cis RA and Br act synergistically to modulate cell viability, with favorable implications for clinical use. In nearly 45% of corticotropinoma-derived primary cultures, the combined administration of 9-cis RA and Br lowered the steady-state level of the ACTH precursor proopiomelanocortin (POMC) more efficiently than either of the drugs alone. In conclusion, the effects of a combination of 9-cis RA and Br on ACTH synthesis/secretion and cell viability in AtT20, and on POMC transcriptional activity in human corticotropinomas might represent a suitable starting point for assessing the potential of this treatment regimen for ACTH-secreting pituitary adenomas. This study thus has potentially important implications for novel therapeutic approaches to CD.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2700744
Anti-GCGR (N-terminal) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4501309
Anti-GR antibody produced in rabbit, affinity isolated antibody
SAB4501310
Anti-GR antibody produced in rabbit, affinity isolated antibody
SAB4501311
Anti-GR antibody produced in rabbit, affinity isolated antibody
SAB1409153
Anti-GSR antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA001538
Anti-GSR antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1410585
Anti-GSR antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
HPA004248
Anti-NR3C1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2101649
Anti-NR3C1 antibody produced in rabbit, affinity isolated antibody
SAB1408583
Anti-NR3C1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB4800041
Imprint® Monoclonal Anti-GR antibody produced in mouse, purified antibody, buffered aqueous solution
SAB1403744
Monoclonal Anti-DRD2, (N-terminal) antibody produced in mouse, clone 1B11, ascites fluid
SAB4200182
Monoclonal Anti-Glutathione Reductase antibody produced in mouse, ~1.0 mg/mL, clone GR6, purified immunoglobulin
WH0002936M1
Monoclonal Anti-GSR antibody produced in mouse, clone 6B4, purified immunoglobulin, buffered aqueous solution
WH0002908M1
Monoclonal Anti-NR3C1 antibody produced in mouse, clone 2C8, purified immunoglobulin, buffered aqueous solution
SAB5300231
Monoclonal Anti-NR3C1 antibody produced in mouse, clone 6E6, ascites fluid