Involvement of bone morphogenetic protein-6 in differential regulation of aldosterone production by angiotensin II and potassium in human adrenocortical cells

Endocrinology
Kenichi InagakiHirofumi Makino

Abstract

Aldosterone production is modified by several growth factors that reside in the adrenal. We have recently reported the existence of a bone morphogenetic protein (BMP) system in human adrenocortical cells, in which BMP-6 augments aldosterone synthesis. Here, we investigated functional roles of BMP-6, focusing on the differential regulation of aldosterone synthesis induced by angiotensin (Ang) II and potassium (K). In human adrenocortical H295R cells, BMP-6 augmented Ang II-induced CYP11B2 transcription and mRNA and aldosterone production but had no effect on K-induced aldosterone production. Inhibition of endogenous BMP-6 action by neutralizing antibodies impaired aldosterone production induced by Ang II but not that induced by K. Blockage of ligand-receptor binding using extracellular domain (ECD) of BMP type I receptors revealed that ECDs to activin receptor-like kinase (ALK)-2 and ALK-3 significantly reduced the aldosterone production induced by Ang II. None of the type I-receptor ECDs tested had any effect on K-induced aldosterone levels. Overexpression of a dominant negative-activin type II receptor construct selectively decreased Ang II-induced aldosterone production without having any effect on K-induced aldosterone produ...Continue Reading

Citations

Jun 2, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Jiro SuzukiHirofumi Makino
Oct 31, 2009·Endocrine Journal·Fumio Otsuka
Jul 29, 2009·The Journal of Endocrinology·Hiroyuki OtaniHirofumi Makino
Apr 28, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Yoshinori MatsumotoHirofumi Makino
Mar 1, 2012·Molecular and Cellular Endocrinology·Tomoko MiyoshiHirofumi Makino
Apr 19, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Takayuki HaraHirofumi Makino
Aug 1, 2013·American Journal of Physiology. Endocrinology and Metabolism·Johannes HoflandFrank H de Jong
Jul 13, 2021·The Journal of Sexual Medicine·Skyler HowellMohit Khera
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

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