TY - JOUR
T1 - Voltage-gated calcium channels in the human adrenal and primary aldosteronism
AU - Felizola, Saulo J.A.
AU - Maekawa, Takashi
AU - Nakamura, Yasuhiro
AU - Satoh, Fumitoshi
AU - Ono, Yoshikiyo
AU - Kikuchi, Kumi
AU - Aritomi, Shizuka
AU - Ikeda, Keiichi
AU - Yoshimura, Michihiro
AU - Tojo, Katsuyoshi
AU - Sasano, Hironobu
N1 - Funding Information:
This work was partly supported by the Takeda Science Foundation (Japan) and the grant for Research on Intractable Diseases from Japanese Ministry of Health, Labour and Welfare .
PY - 2014/10
Y1 - 2014/10
N2 - Calcium channel blockers can efficiently be used in the treatment of primary aldosteronism (PA) related hypertension, but details on the localization of calcium channel (CC) in the human adrenal and its disorders, including PA, have remained unclear. Therefore, in this study we analyzed the known α subunits of L-, N- and T-type CCs in 74 adrenocortical aldosterone-producing adenomas (APA) and 16 cortisol-producing adenomas (CPA) using quantitative RT-PCR (qPCR). We also examined the status of L-(CaV1.2, CaV1.3), N-(CaV2.2) and T-(CaV3.2) CC subunits in five non-pathological adrenals (NA), five idiopathic hyperaldosteronism (IHA) cases, and 50 APA using immunohistochemistry. After qPCR evaluation, only CaV1.2, CaV1.3, CaV2.2, and CaV3.2 mRNA levels could be detected in APA and CPA. Among those, only CaV3.2 mRNA levels were significantly correlated with plasma aldosterone levels (P = 0.0031), CYP11B2 expression levels (P < 0.0001) and the presence of KCNJ5 mutations (P = 0.0019) in APA. The immunolocalization of CCs in NA and IHA was detected in the zona glomerulosa (ZG), with a predominance of CaV3.2 in APA. These findings suggest that different types of CC can be involved in calcium-related aldosterone biosynthesis.
AB - Calcium channel blockers can efficiently be used in the treatment of primary aldosteronism (PA) related hypertension, but details on the localization of calcium channel (CC) in the human adrenal and its disorders, including PA, have remained unclear. Therefore, in this study we analyzed the known α subunits of L-, N- and T-type CCs in 74 adrenocortical aldosterone-producing adenomas (APA) and 16 cortisol-producing adenomas (CPA) using quantitative RT-PCR (qPCR). We also examined the status of L-(CaV1.2, CaV1.3), N-(CaV2.2) and T-(CaV3.2) CC subunits in five non-pathological adrenals (NA), five idiopathic hyperaldosteronism (IHA) cases, and 50 APA using immunohistochemistry. After qPCR evaluation, only CaV1.2, CaV1.3, CaV2.2, and CaV3.2 mRNA levels could be detected in APA and CPA. Among those, only CaV3.2 mRNA levels were significantly correlated with plasma aldosterone levels (P = 0.0031), CYP11B2 expression levels (P < 0.0001) and the presence of KCNJ5 mutations (P = 0.0019) in APA. The immunolocalization of CCs in NA and IHA was detected in the zona glomerulosa (ZG), with a predominance of CaV3.2 in APA. These findings suggest that different types of CC can be involved in calcium-related aldosterone biosynthesis.
KW - Adrenal cortex
KW - Aldosterone
KW - Aldosterone producing adenoma
KW - Calcium channel
KW - Immunohistochemistry
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U2 - 10.1016/j.jsbmb.2014.08.012
DO - 10.1016/j.jsbmb.2014.08.012
M3 - Article
C2 - 25151951
AN - SCOPUS:84906861307
SN - 0960-0760
VL - 144
SP - e410-e416
JO - Journal of Steroid Biochemistry
JF - Journal of Steroid Biochemistry
IS - PART B
ER -
