Regulators of G-protein signaling 4 in adrenal gland: localization, regulation, and role in aldosterone secretion

Regulators of G-protein signaling (RGS proteins) interact with Gα subunits of heterotrimeric G-proteins, accelerating the rate of GTP hydrolysis and finalizing the intracellular signaling triggered by the G-protein-coupled receptor (GPCR)–ligand interaction. Angiotensin II (Ang II) interacts with it...

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Veröffentlicht in:Journal of endocrinology 2007-08, Vol.194 (2), p.429-440
Hauptverfasser: Romero, Damian G, Zhou, Ming Yi, Yanes, Licy L, Plonczynski, Maria W, Washington, Tanganika R, Gomez-Sanchez, Celso E, Gomez-Sanchez, Elise P
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container_end_page 440
container_issue 2
container_start_page 429
container_title Journal of endocrinology
container_volume 194
creator Romero, Damian G
Zhou, Ming Yi
Yanes, Licy L
Plonczynski, Maria W
Washington, Tanganika R
Gomez-Sanchez, Celso E
Gomez-Sanchez, Elise P
description Regulators of G-protein signaling (RGS proteins) interact with Gα subunits of heterotrimeric G-proteins, accelerating the rate of GTP hydrolysis and finalizing the intracellular signaling triggered by the G-protein-coupled receptor (GPCR)–ligand interaction. Angiotensin II (Ang II) interacts with its GPCR in adrenal zona glomerulosa cells and triggers a cascade of intracellular signals that regulates steroidogenesis and proliferation. On screening for adrenal zona glomerulosa-specific genes, we found that RGS4 was exclusively localized in the zona glomerulosa of the rat adrenal cortex. We studied RGS4 expression and regulation in the rat adrenal gland, including the signaling pathways involved, as well as the role of RGS4 in steroidogenesis in human adrenocortical H295R cells. We reported that RGS4 mRNA expression in the rat adrenal gland was restricted to the adrenal zonal glomerulosa and upregulated by low-salt diet and Ang II infusion in rat adrenal glands in vivo. In H295R cells, Ang II caused a rapid and transient increase in RGS4 mRNA levels mediated by the calcium/calmodulin/calmodulin-dependent protein kinase and protein kinase C pathways. RGS4 overexpression by retroviral infection in H295R cells decreased Ang II-stimulated aldosterone secretion. In reporter assays, RGS4 decreased Ang II-mediated aldosterone synthase upregulation. In , RGS4 is an adrenal gland zona glomerulosa-specific gene that is upregulated by aldosterone secretagogues, in vivo and in vitro, and functions as a negative feedback of Ang II-triggered intracellular signaling. Alterations in RGS4 expression levels or functions may be involved in deregulations of Ang II signaling and abnormal aldosterone secretion.
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Angiotensin II (Ang II) interacts with its GPCR in adrenal zona glomerulosa cells and triggers a cascade of intracellular signals that regulates steroidogenesis and proliferation. On screening for adrenal zona glomerulosa-specific genes, we found that RGS4 was exclusively localized in the zona glomerulosa of the rat adrenal cortex. We studied RGS4 expression and regulation in the rat adrenal gland, including the signaling pathways involved, as well as the role of RGS4 in steroidogenesis in human adrenocortical H295R cells. We reported that RGS4 mRNA expression in the rat adrenal gland was restricted to the adrenal zonal glomerulosa and upregulated by low-salt diet and Ang II infusion in rat adrenal glands in vivo. In H295R cells, Ang II caused a rapid and transient increase in RGS4 mRNA levels mediated by the calcium/calmodulin/calmodulin-dependent protein kinase and protein kinase C pathways. RGS4 overexpression by retroviral infection in H295R cells decreased Ang II-stimulated aldosterone secretion. In reporter assays, RGS4 decreased Ang II-mediated aldosterone synthase upregulation. In , RGS4 is an adrenal gland zona glomerulosa-specific gene that is upregulated by aldosterone secretagogues, in vivo and in vitro, and functions as a negative feedback of Ang II-triggered intracellular signaling. 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RGS4 overexpression by retroviral infection in H295R cells decreased Ang II-stimulated aldosterone secretion. In reporter assays, RGS4 decreased Ang II-mediated aldosterone synthase upregulation. In , RGS4 is an adrenal gland zona glomerulosa-specific gene that is upregulated by aldosterone secretagogues, in vivo and in vitro, and functions as a negative feedback of Ang II-triggered intracellular signaling. Alterations in RGS4 expression levels or functions may be involved in deregulations of Ang II signaling and abnormal aldosterone secretion.</abstract><cop>England</cop><pub>BioScientifica</pub><pmid>17641290</pmid><doi>10.1677/JOE-07-0153</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Aldosterone - metabolism
Aldosterone - secretion
Angiotensin II - metabolism
Angiotensin II - pharmacology
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cell Line
Diet, Sodium-Restricted
Female
Genetic Vectors - administration & dosage
GTP-Binding Proteins - metabolism
Humans
Male
Middle Aged
Protein Kinase C - metabolism
Rats
Rats, Sprague-Dawley
Regular papers
Retroviridae - genetics
Reverse Transcriptase Polymerase Chain Reaction
RGS Proteins - genetics
RNA, Messenger - analysis
Signal Transduction - physiology
Transduction, Genetic
Up-Regulation
Zona Glomerulosa - chemistry
Zona Glomerulosa - metabolism
Zona Glomerulosa - secretion
title Regulators of G-protein signaling 4 in adrenal gland: localization, regulation, and role in aldosterone secretion
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