Glucocorticoid receptor expression in the human adrenal gland: Is the adrenal cortex itself a glucocorticoid target tissue?

The adrenal cortex is functionally defined by the presence of three distinct cell layers categorized by the expression of specific steroidogenic enzymes. The zona fasciculata of the adrenal gland is the main source of glucocorticoid production. In target tissues they bind to the specific intracellular glucocorticoid receptor, thus modulating the expression of target genes. However, there is no report as to whether the adrenal cortex itself is a glucocorticoid target tissue. The prerequisite for ‘intracortical’ glucocorticoid action would be the presence of the GR. Previously, we have shown the cellular localization of the GR protein in the adrenal gland by immunhistochemistry. The expression of the GR was shown to be strong in the zona reticularis of the adrenal cortex.

By RT-PCR as well as Western blot assays we confirmed the expression of the active GRa isoform in the human adrenal. The preferential expression of the GR in the zona reticularis may indicate a functional role in the regulation of adrenal androgen biosynthesis. A putative GR target gene in the adrenal cortex could be the 3ß-hydroxysteroid dehydrogenase (HSD3B2) gene, since activation of HSD3B2 by glucocorticoids would lead to a reduced adrenal dehydroepiandrosterone synthesis as shown in parallel in vivo experiments.

To further prove the hypothesis we cloned and transfected a promotor sequence of the human HSD3B2 gene in HeLa cells. Our first experiments show a stimulatory effect of the synthetic glucocorticoid dexamethasone on the HSD3B2 promotor activity in transfected HeLa cells.

In this study, we show the expression of the GR in the adrenal cortex and which may indicate an intracortical function in adrenal androgen biosynthesis via the regulation of HSD3B2 as a putative target gene.

Supported by the Deutsche Forschungsgemeinschaft (GRK336) and the Leidenberger-Müller Stiftung.