Expression of progesterone and estradiol receptors in normal adrenal cortex, adrenocortical tumors, and primary pigmented nodular adrenocortical disease

Abstract

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 ERa was evaluated by enzyme immunoassays, real-time RT-PCR, immunohistochemistry, and cytosol-based ligand-binding assays. ERb and aromatase levels were evaluated by real-time RT-PCR. ERa concentrations were low in NA, in adrenal tissues adjacent to ACA (51G33), in ACC (53G78), and lower in ACA (11G11 fmol/mg DNA). Conversely, PR concentrations were high in NA and adrenal tissues adjacent to ACA, at 307G216 fmol/mg DNA, and were even higher in tumors -726G706 fmol/mg DNA in ACA and 1154G1586 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. ERb transcript levels were very high in all samples except those for two ACCs, whereas aromatase levels were low. PR and ERb 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.

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats

“…In adrenal cortex of different species both receptors have been identified, however, the relative expression of both receptor types differs significantly. Contrary to human adrenal cortex, in the rat adrenal cortex ERa mRNA is far more abundant than the ERb [29][30][31][32]. Likewise, in chicken adrenals the relative expression of ERa mRNA was higher than ERb mRNA [33].…”

Antisecretive and Antitumor Activity of Abiraterone Acetate in Human Adrenocortical Cancer: A Preclinical Study

“…In humans, the ratio of the two isoforms is critical for regulating biological responses of PgR in target tissues [26]. The two PgR isoforms are present in normal adrenal tissue and in ACC and have a similar expression rate [27], whereas NCI-H295R cells display a higher expression of PgRB than PgRA [27]. We found that PgRB is predominantly expressed in NCI-H295R cells and that the PgR antagonist mifepristone was able to antagonize AA-induced NCI-H295R cell toxicity in a concentration-dependent manner.…”

Expression of somatostatin, dopamine, progesterone and growth hormone receptor mRNA in canine cortisol-secreting adrenocortical tumours

“…Altered expression of particular hormone receptors could impact on tumour growth and cortisol secretion, which might provide an opportunity for targeted therapy. Increased expression of growth hormone receptor (GHR) and progesterone receptor (PR) has been observed in human cortisol-secreting ATs (Lin et al, 1997;de Cremoux et al, 2008), which might represent an autocrine PR-GHR mechanism, similar to that seen in canine mammary carcinomas (Mol et al, 1995). Overexpression of somatostatin receptors (SSTR1-5) (Mariniello et al, 2011) and the presence of D2-like dopamine receptors (DRD2 and DRD4) have also been reported in human ATs (Pivonello et al, 2004).…”