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Cortisol-Secreting Adrenal Adenomas Express 11β-Hydroxysteroid Dehydrogenase Type-2 Gene yet Possess Low 11β-HSD2 Activity
  1. Giuseppina Mazzocchi,
  2. Francesco Aragona,
  3. Ludwik K. Malendowicz,
  4. Lucia Gottardo,
  5. Gastone G. Nussdorfer
  1. From the Department of Human Anatomy and Physiology, Section of Anatomy (G.M., L.G., G.G.N.) University of Padua, Italy
  2. Department of Oncological and Surgical Sciences (F.A.), School of Medicine, University of Padua, Italy;
  3. Department of Histology and Embryology (L.K.M.), Poznan School of Medicine, Poland.
  1. Address correspondence to: G.G. Nussdorfer, Department of Human Anatomy and Physiology, Section of Anatomy, Via Gabelli 65, I-35121 Padova, Italy. E-mail ggnanat{at}ipdunidx.unipd.it

Abstract

Background 11β-hydroxysteroid dehydrogenase Type-2 (11β-HSD2) is an unidirectional enzyme that catalyzes the conversion of glucocorticoid hormones cortisol and corticosterone (B) into their corresponding inactive forms, cortisone, and 11-dehydrocorticosterone (DH-B). We have provided evidence that 11β-HSD2 is expressed as messenger RNA (mRNA) and protein in human adrenocortical cells, where its activity is inhibited in vitro by the main glucocorticoid agonists, adrenocorticotropic hormone (ACTH) and angiotensin-II. It seemed worthwhile, therefore, to study the gene expression and activity of 11β-HSD2 in cortisol-secreting adrenocortical adenomas.

Methods Three adrenal adenomas that produced Cushing syndrome were recruited. Three normal adrenal glands were obtained from patients who underwent unilateral nephrectomy with ipsilateral adrenalectomy for renal cancer. 11β-HSD2 gene expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) in adenoma and normal adrenocortical tissue. Cortisol, B, cortisone, and DH-B production by adenoma and adrenal slices in vitro was assayed by quantitative high-performance liquid chromatography (HPLC), and the activity of 11β-HSD2 was evaluated by measuring the conversion of [3H]-cortisol to [3H]-cortisone.

Results RT-PCR allowed the detection of the 11β-HSD2 mRNA in the three adrenal adenomas and normal adrenal cortices examined. Under basal conditions, adenoma slices secreted higher amounts of cortisol and B, but markedly lower amounts of cortisone and DH-B than adrenal slices. ACTH raised cortisol and B production from both specimens, and it lowered cortisone and DH-B yield. The level basal conversion of [3H]-cortisol to [3H]-cortisone was notably less in adenomas than in adrenals, and ACTH decreased it in both tissues.

Conclusions Collectively, our findings indicate that cortisol-secreting adrenal adenomas express the 11β-HSD2 gene, but the activity of the enzyme is suppressed in adenomas when compared with the normal adrenal cortex. We advance the hypothesis that the elevated local concentration of steroid hormones that occur in adenomas down-regulates 11β-HSD2 activity, thereby contributing to their abnormal steroidogenic function.

Key Words
  • Cortisol-secreting adenomas
  • human adrenal cortex
  • 11β-hydroxysteroid dehydrogenase type 2

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