Glucocorticoid Receptor as a Potential Target to Decrease Aromatase Expression and Inhibit Leydig Tumor Growth.

Glucocorticoid Receptor as a Potential Target to Decrease Aromatase Expression and Inhibit Leydig Tumor Growth. Am J Pathol. 2016 Mar 8; Authors: Panza S, Malivindi R, Chemi F, Rago V, Giordano C, Barone I, Bonofiglio D, Gelsomino L, Giordano F, Andò S, Catalano S Abstract Leydig cell tumors are the most frequent interstitial neoplasms of the testis with apparent recent increased incidence. They are hormonally active and are considered one of the steroid-secreting tumors. Although usually benign, the malignant phenotype responds poorly to conventional chemotherapy or radiation, highlighting the need to identify new therapeutic targets for treatment. Here, we identified a novel glucocorticoid-mediated mechanism that controls cell growth in Leydig cell tumors. We found that a synthetic glucocorticoid receptor agonist, dexamethasone, significantly reduces cell proliferation in rat Leydig tumor cells by decreasing the expression and the enzymatic activity of the estrogen-producing enzyme aromatase. This inhibitory effect relies on the ability of activated glucocorticoid receptor to regulate the aromatase gene transcriptional activity through the recruitment of the corepressors nuclear receptor corepressor protein and silencing mediator of retinoid and thyroid hormone receptor to a newly identified putative glucocorticoid responsive element within the aromatase proximal promoter II. Moreover, our in vivo studies reveal a significant red...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research