Steroidogenic Activity of Aldosterone-Producing Adenoma with and without KCNJ5 Gene Mutations, Comparing with that in Each Adherent Normal Tissue
Journal Title: Journal of Endocrinology and Diabetes - Year 2014, Vol 1, Issue 1
Abstract
Introduction: The steroidogenic activity in a KCNJ5-gene mutated aldosterone-producing adenoma (APA) was reported to be much stronger than that in an APA of the wild type, while it is still controversial. Objectives: We examined whether the normal adrenal tissue attached to APA also possesses KCNJ5 gene mutations, and also investigated steroidogenic activity of mutated and non-mutated APA tissue cells with that of each normal tissue cell attached to APA in order to clarify the nature of steroidogenic activity. Methods: We selected 12 patients with and without KCNJ5 gene mutation-harboring APA in whom normal adrenal tissue adhered to the APA. We analyzed the presence of KCNJ5 gene mutations by using those tissues. Results: APA tissues of 6 patients possessed KCNJ5 gene mutations, whereas those mutations were not detected in any of the adjacent normal tissue samples as well as another 6 cases of APA. In two APA tissues with or without KCNJ5 gene mutation, we also compared the steroidogenic activity of isolated cells from each APA tissue with that from the normal adherent tissues. The cortisol production of the mutated APA cells was markedly decreased compared with that of the normal cells, suggesting that the aldosterone production pathway becomes dominant and the cortisol production pathway is downregulated in that APA tissue. Furthermore, the ratio of aldosterone to cortisol in the normal adherent tissue was about 1/4th of that of the wild-type APA tissue, while it was about 1/10th in the mutated APA. Conclusion: KCNJ5 gene mutations in the normal tissue adhering to KCNJ5 gene mutation-harboring APA was not observed, suggesting that somatic mutations of the KCNJ5 gene only occur in APA tissue. It is also suggested that KCNJ5 gene mutations dominantly induce the aldosterone production pathway as well as concomitant decline in cortisol production, resulting in highly autonomous aldosterone production.
Authors and Affiliations
Tetsuo Nishikawa, Yoko Matsuzawa, Takumi Kitamoto, Sachiko Suematsu, Jun Saito, Masao Omura
Keywords
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- EP ID EP332896
- DOI 10.15226/2374-6890/1/1/00103
- Views 105
- Downloads 0
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