TY - JOUR
T1 - 3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma
AU - Konosu-Fukaya, Sachiko
AU - Nakamura, Yasuhiro
AU - Satoh, Fumitoshi
AU - Felizola, Saulo J.A.
AU - Maekawa, Takashi
AU - Ono, Yoshikiyo
AU - Morimoto, Ryo
AU - Ise, Kazue
AU - Takeda, Ken ichiro
AU - Katsu, Koshin
AU - Fujishima, Fumiyoshi
AU - Kasajima, Atsuko
AU - Watanabe, Mika
AU - Arai, Yoichi
AU - Gomez-Sanchez, Elise P.
AU - Gomez-Sanchez, Celso E.
AU - Doi, Masao
AU - Okamura, Hitoshi
AU - Sasano, Hironobu
N1 - Funding Information:
Drs. Gomez-Sanchez are supported by NIH grant RO1HL27255 .
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2015/6/5
Y1 - 2015/6/5
N2 - It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA (P < 0.0001) and plasma aldosterone concentration (PAC) of the patients (P < 0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P < 0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA (P < 0.0001) and HSD3B1 mRNA (P = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA.
AB - It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA (P < 0.0001) and plasma aldosterone concentration (PAC) of the patients (P < 0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P < 0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA (P < 0.0001) and HSD3B1 mRNA (P = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA.
KW - 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1)
KW - 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2)
KW - Aldosterone-producing adenoma (APA)
KW - CYP11B1 (11β-hydroxylase) and KCNJ5
KW - CYP11B2 (aldosterone synthase)
UR - http://www.scopus.com/inward/record.url?scp=84940004637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940004637&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2014.10.008
DO - 10.1016/j.mce.2014.10.008
M3 - Article
C2 - 25458695
AN - SCOPUS:84940004637
SN - 0303-7207
VL - 408
SP - 205
EP - 212
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -