Adrenal
tumors occur more frequently in women and are the leading cause of
Cushing's syndrome during pregnancy. We aimed to evaluate the potential role of sex
steroids in the susceptibility of women to adrenocortical
tumors. We evaluated the presence of the
progesterone receptor (PR),
estradiol receptors (ERs), and
aromatase in 5 patients with primary pigmented nodular adrenal disease (PPNAD), 15
adrenocortical adenomas (ACAs) and adjacent normal tissues, 12
adrenocortical carcinomas (ACCs), and 3 normal adrenal glands (NA). The expression of PR and
ERalpha was evaluated by
enzyme immunoassays, real-time RT-PCR, immunohistochemistry, and cytosol-based
ligand-binding assays.
ERbeta and
aromatase levels were evaluated by real-time RT-PCR.
ERalpha concentrations were low in NA, in adrenal tissues adjacent to ACA (51+/-33), in ACC (53+/-78), and lower in ACA (11+/-11 fmol/mg
DNA). Conversely, PR concentrations were high in NA and adrenal tissues adjacent to ACA, at 307+/-216 fmol/mg
DNA, and were even higher in
tumors - 726+/-706 fmol/mg
DNA in ACA and 1154+/-1586 fmol/mg
DNA in ACC - and in isolated PPNAD nodules. Binding study results in four
tumors were compatible with binding to a
steroid receptor. In patients with PPNAD, a strong positive immunohistochemical signal was associated with the sole isolated nodular regions.
ERbeta transcript levels were very high in all samples except those for two ACCs, whereas
aromatase levels were low. PR and
ERbeta are clearly present in normal adrenal glands and adrenal
tumors. Further studies may shed light on the possible pathogenic role of these receptors in adrenal proliferation.