Sphingosine‐1‐phosphate stimulates cortisol secretion

Rábano, Miriam; Peña, Ana; Brizuela, Leyre; Marino, Aída; Macarulla, J. M.; Trueba, Miguel; Gómez-Muñoz, Antonio

doi:10.1016/s0014-5793(02)03882-6

Cited by 41 publications

(43 citation statements)

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“…Both of these pathways are essential for many of the biological functions that are regulated by S1P (6,11,12). In particular, PI3K and ERK have been implicated in the stimulation of steroidogenesis by different agonists (3,(13)(14)(15)(16)(17)(18), and we found that S1P is also a potent stimulator of cortisol secretion (19).…”

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confidence: 52%

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Brizuela

Rábano

Gangoiti

et al. 2007

Journal of Lipid Research

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We reported recently that sphingosine-1-phosphate (S1P) is a novel regulator of aldosterone secretion in zona glomerulosa cells of adrenal glands and that phospholipase D (PLD) is implicated in this process. We now show that S1P causes the phosphorylation of protein kinase B (PKB) and extracellularly regulated kinases 1/2 (ERK 1/2), which is an indication of their activation, in these cells. These effects are probably mediated through the interaction of S1P with the Gi protein-coupled receptors S1P1/3, as pretreatment with pertussis toxin or with the S1P1/3 antagonist VPC 23019 completely abolished the phosphorylation of these kinases. Inhibitors of phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase kinase (MEK) blocked S1P-stimulated aldosterone secretion. This inhibition was only partial when the cells were incubated independently with inhibitors of each pathway. However, aldosterone output was completely blocked when the cells were pretreated with LY 294002 and PD 98059 simultaneously. These inhibitors also blocked PLD activation, which indicates that this enzyme is downstream of PI3K and MEK in this system. We propose a working model for S1P in which stimulation of the PI3K/PKB and MEK/ERK pathways leads to the stimulation of PLD and aldosterone secretion.-Brizuela, L., M. Rábano, P. Gangoiti, N. Narbona, J. M. Macarulla, M. Trueba, and A. Gómez-Muñ oz. Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways. J. Lipid Res.

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confidence: 52%

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Brizuela

Rábano

Gangoiti

et al. 2007

Journal of Lipid Research

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“…Others have shown that S1P stimulates cortisol secretion in zona fasciculata bovine adrenal cells in a PKC and Ca 2+ -dependent manner (Rabano et al, 2003). In addition to stimulating cortisol There have been many other reports of the stimulatory and inhibitory effects of bioactive sphingolipids on steroid hormone biosynthesis in both gonadal and adrenal cell lines (Budnick et al, 1999;Degnan et al, 1996;Kwun et al, 1999;McClellan et al, 1997;Meroni et al, 2000;Porn et al, 1991;Rabano et al, 2003;Santana et al, 1996). Increased ceramide levels stimulate progesterone synthesis in both MA-10 murine Leydig cells (Kwun et al, 1999) and JEG-3 human choriocarcinoma cells (McClellan et al, 1997).…”

Section: Bioactive Sphingolipids In Steroidogenesismentioning

confidence: 97%

“…S1P activates a cascade of events culminating in the binding of the sterol regulatory element binding protein-1 (SREBP-1) to the promoter of CYP17, the activation of transcription, and increased cortisol biosynthesis. Others have shown that S1P stimulates cortisol secretion in zona fasciculata bovine adrenal cells in a PKC and Ca 2+ -dependent manner (Rabano et al, 2003). In addition to stimulating cortisol secretion, S1P has been recently found to increase aldosterone production via a protein kinase C and phospholipase D-dependent pathway (Brizuela et al, 2006).…”

Section: Bioactive Sphingolipids In Steroidogenesismentioning

confidence: 99%

“…S1P activates a cascade of events culminating in the binding of the sterol regulatory element binding protein-1 (SREBP-1) to the promoter of CYP17, the activation of transcription, and increased cortisol biosynthesis. Others have shown that S1P stimulates cortisol secretion in zona fasciculata bovine adrenal cells in a PKC and Ca 2+ -dependent manner (Rabano et al, 2003). In addition to stimulating cortisol There have been many other reports of the stimulatory and inhibitory effects of bioactive sphingolipids on steroid hormone biosynthesis in both gonadal and adrenal cell lines (Budnick et al, 1999;Degnan et al, 1996;Kwun et al, 1999;McClellan et al, 1997;Meroni et al, 2000;Porn et al, 1991;Rabano et al, 2003;Santana et al, 1996).…”

Section: Bioactive Sphingolipids In Steroidogenesismentioning

confidence: 99%

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Steroidogenic factor-1 is a sphingolipid binding protein

Urs

Dammer

Kelly

et al. 2007

Molecular and Cellular Endocrinology

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Steroidogenic factor (SF1, NR5A1, Ad4BP) is an orphan nuclear receptor that is essential for steroid hormone-biosynthesis and endocrine development. Studies have found that the ability of this receptor to increase target gene expression can be regulated by post-translational modification, subnuclear localization, and protein-protein interactions. Recent crystallographic studies and our mass spectrometric analyses of the endogenous receptor have demonstrated an integral role for ligandbinding in the control of SF1 transactivation activity. Herein, we discuss our findings that sphingosine is an endogenous ligand for SF1. These studies and the structural findings of others have demonstrated that the receptor can bind both sphingolipids and phospholipids. Thus, it is likely that multiple bioactive lipids are ligands for SF1 and that these lipids will differentially act to control SF1 activity in a context-dependent manner. Finally, these findings highlight a central role for bioactive lipids as mediators of trophic-hormone stimulated steroid hormone biosynthesis. Keywordssteroidogenic factor-1; CYP17; sphingosine; cAMP; adrenocorticotropin Regulation of SF1 activitySteroid hormone biosynthesis involves the concerted action of a group of proteins that regulate substrate delivery and metabolism. Both the activity and expression of these enzymes is controlled by the integration of signaling pathways. One of these signal transduction pathways involves the activation of the cAMP-dependent protein kinase (PKA). A consequence of PKA activation is increased transcription of steroidogenic genes. This increase in transcription is mediated by the binding of various transcription factors, including SF1, to cAMP responsive sequences in the promoters of steroidogenic genes (Sewer and Waterman, 2001;Sewer and Waterman, 2003). SF1 is a nuclear receptor that plays a key role not only in steroidogenesis (Bakke et al., 2001), but also in endocrine development and sex differentiation (Hammer et al., 2005;Parker et al., 2002).Many laboratories have carried out research to determine the mechanism by which SF1 activates steroidogenic gene transcription. Although transcription of steroidogenic genes Corresponding author: Marion B. Sewer, School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, Tel: (404) Fax: (404) 894-0519; E-mail: marion.sewer@biology.gatech.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Bioactive sphingolipids in steroidogenesisSphingolipids are a diverse family of amphiphatic molecules that are comprised of a long-chain ...

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“…Among the possible effectors of adrenal steroidogenesis, increased levels of fatty acids or other lipid metabolites, within the adrenal cortex, could be involved in the dysregulation of basal corticosterone production (Sarel & Widmaier 1995, Rabano et al 2003. In addition, the regulation of steroidogenesis by adipocyte secretory products generated by fat cells detected in close contact with steroidogenic cells has also been shown (Ehrhart-Bornstein et al 2003).…”

Section: Weeks Of Treatmentmentioning

confidence: 99%

Insulin sensitization with a peroxisome proliferator-activated receptor γ agonist prevents adrenocortical lipid infiltration and secretory changes induced by a high-sucrose diet

Calejman¹,

Gruccio²,

Mercau³

et al. 2012

Journal of Endocrinology

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It has been hypothesized that deviations in glucocorticoid secretion and/or action may contribute to somatic and biochemical changes observed in patients with and animal models of insulin resistance (IR). In this study, we analyzed changes in rat adrenocortical function and morphology associated with the development of IR, generated in male adult rats by the addition of 30% sucrose to the drinking water. Caloric intake, body and adipose tissue weights, and biochemical parameters associated with IR were determined. Expression levels of Star, Cyp11A1, Mc2r, Pparg (Pparg), and Cd36 were evaluated by real-time PCR, histochemical analysis of the adrenal cortex was performed using Masson's trichrome and Sudan III staining, and corticosterone levels were measured by RIA. After 7 weeks of sucrose administration, higher serum glucose, insulin, and triglyceride levels and an altered glycemic response to an i.p. insulin test were detected. Adrenal glands showed a neutral lipid infiltration. An increase in Star, Cyp11A1, Mc2r, Pparg and Cd36 and a decrease in Mc2r levels were also found. Furthermore, sucrose-treated animals exhibited higher basal corticosterone levels and a blunted response to ACTH injection. Noteworthy, the adrenocortical (functional and histological) abnormalities were prevented in sucrose-treated rats by the simultaneous administration of an insulin-sensitizing PPARg agonist. In conclusion, sucrose-induced IR affects adrenocortical morphology and function possibly via the generation of adipokines or lipid metabolites within the adrenal gland. These abnormalities are prevented by the administration of a PPARg agonist by mechanisms involving both extra-and intraadrenal effects.

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Sphingosine‐1‐phosphate stimulates cortisol secretion

Cited by 41 publications

References 38 publications

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways

Steroidogenic factor-1 is a sphingolipid binding protein

Insulin sensitization with a peroxisome proliferator-activated receptor γ agonist prevents adrenocortical lipid infiltration and secretory changes induced by a high-sucrose diet

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