Expression of aromatase and estrogen receptors in human adrenocortical tumors

We recently demonstrated that adrenocortical carcinoma cells express aromatase and estrogen receptors (ERs) and that 17 beta-estradiol enhances adrenocortical cell proliferation. To provide a clue to the role of estrogens in adrenal tumorigenesis, we investigated the expression profile of genes involved in sex steroid hormone production and activity in a large series of normal and neoplastic human adrenocortical tissues. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry showed that ER alpha and ER beta, androgen receptor (AR), and aromatase were expressed in the adrenal cortex and in adrenocortical tumors. ER beta was the predominant ER subtype and was mainly expressed in the zona glomerulosa and fasciculata. Western blot analysis revealed the presence of a truncated form of AR in adrenocortical tissues. With respect to the normal adrenal cortex and adrenocortical adenomas, carcinomas were characterized by significantly lower ER beta levels, ER alpha upregulation, and aromatase overexpression. ER expression correlated with expression of nuclear hormone receptors, suggesting they could be involved in ER modulation. In agreement with our in vitro findings, the results of this study suggest that estrogens, locally produced by aromatase, could enhance adrenocortical cell proliferation though autocrine/paracrine mechanisms. This study opens new perspectives on the potential use of antiestrogens and aromatase inhibitors as therapeutic agents against ACC.