An in vivo role of bone morphogenetic protein-6 in aldosterone production by rat adrenal gland

Yoshinori Matsumoto, Fumio Otsuka, Kenichi Inagaki, Naoko Yamauchi, Mariko Narazaki, Tomoko Miyoshi, Eri Nakamura, Kanako Ogura-Ochi, Masaya Takeda, Hirofumi Makino

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex. We previously reported the presence of a functional BMP system including BMP-6 in human adrenocortical cells. BMP-6 contributes to Ang II-induced aldosterone production by activating Smad signaling, in which endogenous BMP-6 action is negatively controlled by Ang II in vitro. In the present study, we examined the in vivo role of BMP-6 in regulation of aldosterone by neutralizing endogenous BMP-6 in rats treated with immunization against BMP-6. Three-week-old male rats were actively immunized with rat mature BMP-6 antigen conjugated with keyhole limpet hemocyanin (KLH). The immunization treatment had no effect on bilateral adrenal weight or its ratio to body weight. Urinary aldosterone excretion was time-dependently increased during the 8-week observation period in the control group. Of note, the level of urinary aldosterone excretion in BMP-6-KLH-immunized rats was significantly reduced compared to that in the control group, suggesting that endogenous BMP-6 contributes to the induction of aldosterone production in vivo. Moreover, the level of urinary aldosterone/creatinine after 8-week treatment was significantly lowered by treatment with BMP-6-KLH. In contrast, with chronic Ang II treatment, urinary aldosterone and creatinine-corrected values at 8 weeks were not significantly different between the two groups, suggesting that the effects of BMP-6-KLH were impaired under the condition of chronic treatment with Ang II. The mRNA levels of Cyp11b2, but not those of Star, P450scc and 3βhsd2, were significantly decreased in adrenal tissues isolated from BMP-6-KLH-immunized rats after 8-week treatment. Furthermore, the ratio of plasma aldosterone level to corticosterone was significantly decreased by immunization with BMP-6-KLH. Collectively, the results indicate that endogenous BMP-6 is functionally linked to aldosterone synthesis by the zona glomerulosa in the adrenal cortex in vivo.

Original languageEnglish
Pages (from-to)8-14
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number1-2
Publication statusPublished - Oct 2012


  • Adrenal
  • Aldosterone
  • Angiotensin
  • Bone morphogenetic protein
  • CYP11B2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'An in vivo role of bone morphogenetic protein-6 in aldosterone production by rat adrenal gland'. Together they form a unique fingerprint.

Cite this