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Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations

Jung Soo Lim1,2, Samuel W Plaska1, Juilee Rege1

  • 1Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States.

Frontiers in Endocrinology
|April 2, 2021
PubMed
Abstract

Insights

Aldosterone-producing adenomas (APAs) show varying responses to hormones based on their genetic mutations. APAs with ATPase mutations appear more sensitive to ACTH than those with KCNJ5 mutations.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Somatic gene mutations causing increased intracellular calcium are common in aldosterone-producing adenomas (APAs).
  • Angiotensin II and ACTH are known to stimulate aldosterone production in APAs.
  • Limited data exists on how different APA mutations affect hormonal response.

Purpose of the Study:

  • To investigate the transcript expression of key receptors (AGTR1, MC2R, MRAP) in APAs with specific aldosterone-driver mutations.
  • To understand the differential expression of these receptors in relation to known APA genetic alterations.

Main Methods:

  • RNA analysis of APAs with KCNJ5, ATP1A1, CACNA1D, and ATP2B3 mutations, alongside normal adrenal tissue.
  • Quantitative RT-PCR was used to measure transcript levels of MC2R, MRAP, AGTR1, CYP11B2, CYP17A1, and CYP11B1.

Main Results:

  • APAs exhibited significantly higher CYP11B2, MC2R, and AGTR1 transcript levels compared to normal adrenal tissue.
  • Lower MRAP, CYP17A1, and CYP11B1 transcript levels were observed in APAs.
  • MC2R and CYP11B2 transcripts were lower in KCNJ5-mutated APAs compared to other mutation types.

Conclusions:

  • MC2R and AGTR1 are expressed in all APAs, but expression levels vary based on underlying somatic mutations.
  • APAs with ATPase mutations demonstrate a greater responsiveness to ACTH compared to those with KCNJ5 mutations.
Keywords:
adrenaladrenal cortexadrenocorticotropic hormone (ACTH)aldosteroneangiotensinprimary aldosteronism

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