Repression of DAX-1 and Induction of SF-1 Expression

Osman, Hanan; Murigande, Claire; Nadakal, Anne; Capponi, Alessandro M.

doi:10.1074/jbc.m206595200

Cited by 47 publications

(8 citation statements)

References 51 publications

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“…These results are consistent with earlier reports [41][42][43]. Erik Willems et al suggested that FSK acted on the expression of SF-1 mRNA at the transcriptional level, and this was determined to be possible because FSK-induced enhanced expression of SF-1 mRNA was almost completely abolished by actinomycin D [39]. Furthermore, multiple SF-1 binding sites are present in the CYP11A1 promoter [44] and the StAR promoter [45].…”

Section: Discussionsupporting

confidence: 82%

“…FSK is a mimic of an adrenocorticotropic hormone mode of action. It has been previously reported that FSK dramatically increased SF-1 protein and mRNA levels by repressing DAX-1 protein and mRNA expression [39]. The clinical study also observed the role of FSK in significantly increasing lean muscle mass, bone mass, and testosterone in overweight and obese men [40].…”

Section: Discussionsupporting

confidence: 54%

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Directed Mouse Embryonic Stem Cells into Leydig-Like Cells Rescue Testosterone-Deficient Male Rats In Vivo

Yang

et al. 2015

Stem Cells and Development

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 54%

Directed Mouse Embryonic Stem Cells into Leydig-Like Cells Rescue Testosterone-Deficient Male Rats In Vivo

Yang

et al. 2015

Stem Cells and Development

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“…Although the StAR gene lacks cAMP-responsible element (CRE) recognition sites in its promoter region (39), cAMP is one of the most potent activators of the StAR promoter, probably acting through CCAT/enhancer binding protein (C/EBP) response elements (39 -41). Induction of the StAR protein expression also directly correlates with inhibition of the dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X-chromosome, gene 1 (DAX-1) and activation of steroidogenic factor 1 (SF-1) transcription factors (42). However, in our experiments, PKG II activated aldosterone release from ZG cells but, in contrast to PKA, did not stimulate StAR gene expression (Fig.…”

Section: Activation Of Pkg II In Zg Cells Increased Aldosterone Producontrasting

confidence: 46%

cGMP-dependent Protein Kinase Type II Regulates Basal Level of Aldosterone Production by Zona Glomerulosa Cells without Increasing Expression of the Steroidogenic Acute Regulatory Protein Gene

Gambaryan¹,

Butt²,

Marcus

et al. 2003

Journal of Biological Chemistry

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The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of salt and water homeostasis. Here, we demonstrate the expression and functional role of cGMP-dependent protein kinases (PKGs) in rat adrenal cortex. Expression of PKG II is restricted to adrenal zona glomerulosa (ZG) cells, whereas PKG I is localized to the adrenal capsule and blood vessels. Activation of the aldosterone system by a low sodium diet up-regulated the expression of PKG II, however, it did not change PKG I expression in adrenal cortex. Both, activation of PKG II in isolated ZG cell and adenoviral gene transfer of wild type PKG II into ZG cells enhanced aldosterone production. In contrast, inhibition of PKG II as well as infection with a PKG II catalytically inactive mutant had an inhibitory effect on aldosterone production. Steroidogenic acute regulatory (StAR) protein that regulates the rate-limiting step in steroidogenesis is a new substrate for PKG II and can be phosphorylated by PKG II in vitro at serine 55/56 and serine 99. Stimulation of aldosterone production by PKG II in contrast to stimulation by PKA did not activate StAR gene expression in ZG cells. The results presented indicate that PKG II activity in ZG cells is important for maintaining basal aldosterone production.The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of salt and water homeostasis by promoting the constriction of arterioles within the renal and systemic circulation and reabsorption of sodium in proximal segments of the nephron through angiotensin II (Ang II).1 Ang II also stimulates aldosterone production from adrenal zona glomerulosa (ZG), which promotes the reabsorption of sodium, by activating sodium-potassium ATPases and epithelial sodium channels (reviewed in Ref.1).Regulation of aldosterone production is under the multifunctional control of different factors among which the most important are adrenocorticotropin (ACTH), Ang II, and K ϩ . These factors utilize a variety of transduction mechanisms, including activation of cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and regulation of cytosolic free calcium.Acute stimulation of steroid production requires both the synthesis of new proteins and protein phosphorylation. The delivery of the steroid substrate cholesterol from the outer to the inner mitochondrial membrane, a process mediated by the steroidogenic acute regulatory protein (StAR), represents the rate-limiting step for the production of aldosterone and other steroids (reviewed in Ref. 2). StAR is a phosphoprotein that has several putative phosphorylation sites for different protein kinases (cAMP-and cGMP-dependent protein kinases, PKC). However, until now only PKA-specific phosphorylation at serine 56 and serine 194 of StAR has been demonstrated and shown to increase the delivery of sterol substrate and, in part, to account for the immediate effects of cAMP on steroid production (3).Although multiple factors control aldosterone production, only natriuretic peptides (NPs) and nitric oxid...

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“…Likewise, several additional signaling pathways have also been demonstrated to play important roles in regulating StAR expression. These include calcium regulated transduction systems [59,[86][87][88][89][90], arachidonic acid metabolites [91,92], chloride ion channels [93,94], and mitogen activated protein Kinase (MAPK)/extracellular signal-related kinases (ERKs) [95,96].…”

Section: Regulation Of Star Expressionmentioning

confidence: 99%

Regulation of the Steroidogenic Acute Regulatory Protein Expression: Functional and Physiological Consequences

Manna

Stocco²

2005

curr drug targets immune endocr metabol disord

123

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Steroid hormones are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta and brain and are essential for normal reproductive function and bodily homeostasis. The rate-limiting and regulated step in steroid biosynthesis is the intramitochondrial transport of cholesterol, a process that is mediated by the steroidogenic acute regulatory (StAR) protein. The importance of StAR has been illustrated by analyses of patients with lipoid congenital adrenal hyperplasia (lipoid CAH), an autosomal recessive disorder that markedly disrupts the synthesis of all gonadal and adrenal steroids. Molecular and physio-pathological analyses have demonstrated that alterations in the StAR gene are the only known cause of lipoid CAH. Furthermore, StAR knockout mice have been generated and display a phenotype that is essentially identical to the human condition. Recent advances in tissue-specific and hormone-induced expression of the StAR protein provide insights into a number of human endocrinological health issues including developmental and reproductive abnormalities. Several factors and processes have been demonstrated to influence StAR expression in steroidogenic cells and there is increasing evidence that a transcription factor-binding site-rich region present in the proximal region of the StAR promoter is highly instrumental in StAR gene expression. In this review we focus on the significant findings that have been made with regards to the regulation of StAR expression and also on the clinical and endocrinological consequences of a non-functioning StAR gene.

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Repression of DAX-1 and Induction of SF-1 Expression

Cited by 47 publications

References 51 publications

Directed Mouse Embryonic Stem Cells into Leydig-Like Cells Rescue Testosterone-Deficient Male Rats In Vivo

Directed Mouse Embryonic Stem Cells into Leydig-Like Cells Rescue Testosterone-Deficient Male Rats In Vivo

cGMP-dependent Protein Kinase Type II Regulates Basal Level of Aldosterone Production by Zona Glomerulosa Cells without Increasing Expression of the Steroidogenic Acute Regulatory Protein Gene

Regulation of the Steroidogenic Acute Regulatory Protein Expression: Functional and Physiological Consequences

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