The role of SF-1/Ad4BP in the control of the bovine gene for the steroidogenic acute regulatory (StAR) protein

Rust, Werner; Stedronsky, Katrin; Tillmann, G.; Morley, Steven D.; Walther, Norbert; Ivell, Richard

doi:10.1677/jme.0.0210189

Cited by 57 publications

(30 citation statements)

References 33 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, although SF1 and LRH1 are weak activators of the Star promoter in MA-10 Leydig cells, they can also cooperate with c-JUN as do NR4A members (NUR77, NURR1, NOR1). The weak activation by SF1 and LRH1 may be explained by the already high levels of these factors in MA-10 cells (Zhang & Mellon 1997, Daggett et al 2000, Aesoy et al 2002 since in heterologous cells that do not express SF1, SF1 can activate the Star promoter (Sugawara et al 1996, Rust et al 1998, Reinhart et al 1999, and our unpublished data).…”

Section: Sf1 and Lrh1 Cooperate With C-jun On The Star Promotermentioning

confidence: 58%

The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter

Martin¹,

Tremblay²

2008

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The steroidogenic acute regulatory protein plays an essential role in steroid biosynthesis in steroidogenic cells. It is involved in the transport of cholesterol through the mitochondrial membrane where the first step of steroidogenesis occurs. Star gene expression in testicular Leydig cells is regulated by the pituitary LH through the cAMP signaling pathway. So far, several transcription factors have been implicated in the regulation of Star promoter activity in these cells. These include the nuclear receptors NUR77 and SF1, AP-1 family members (particularly c-JUN), GATA4, C/EBPb, DLX5/6, and CREB. Some of these factors were also shown to act in a cooperative manner to further enhance Star promoter activity. Here, we report that NUR77 and c-JUN have additive effects on the Star promoter. These effects were abolished only when both elements, NUR77 at K95 bp and AP-1 at K78 bp, were mutated. Consistent with this, in vitro co-immunoprecipitation revealed that NUR77 and c-JUN interact and that this interaction is mediated through part of the ligand binding domain of NUR77. Furthermore, we found that SF1 could cooperate with c-JUN on the mouse Star promoter but this cooperation involved different regulatory elements. Collectively, our data not only provide new insights into the molecular mechanisms that control mouse Star transcription in Leydig cells but also reveal a novel mechanism for the regulation of NR4A1-dependent genes in tissues where NUR77 and c-JUN factors are co-expressed.

show abstract

Section: Sf1 and Lrh1 Cooperate With C-jun On The Star Promotermentioning

confidence: 58%

The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter

Martin¹,

Tremblay²

2008

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…Since this is generally considered to be a cAMP-mediated event, attention focused on the role of cAMP in the regulation of the StAR gene (Caron et al 1997a, Rust et al 1998, Sandhoff et al 1998, LaVoie et al 1999. Like several other cAMP-regulated genes involved in steroid biosynthesis, the promoter region of the StAR gene lacks an easily recognizable cAMP response element.…”

Section: Regulation Of the Star Genementioning

confidence: 99%

The role of the StAR protein in steroidogenesis: challenges for the future

Stocco¹

2000

Journal of Endocrinology

262

125

View full text Add to dashboard Cite

The steroidogenic acute regulatory or StAR protein has been shown to be instrumental in the acute regulation of steroid hormone biosynthesis through its action in mediating cholesterol transfer to the inner mitochondrial membrane and the cholesterol side chain cleavage enzyme system. Since the time of its cloning in 1994, a number of studies have been performed which underscore the important role that this protein plays in steroidogenesis. While it is now quite apparent that StAR fulfills the criteria for the acute regulator as proposed by early studies, several crucial areas remain poorly understood. This list is topped by the so far intractable nature of the mechanism of action of StAR in transferring cholesterol to the P450scc enzyme. A second area which should prove to be of great interest is that of further understanding the regulation of the StAR gene which, like many genes, is quite complex. Lastly, with the recent demonstration of StAR being present in the brain, determining if StAR has a role in the synthesis of neurosteroids should prove to be of great importance.

show abstract

“…All bovine StAR promoter-reporter DNA constructs, in addition to control vectors, were exactly as previously described (Rust et al 1998). DNA was purified using the EndoFree Plasmid Maxi Kit (Qiagen, Hilden, Germany) as described by the manufacturer.…”

Section: Cell Transfection and Analysismentioning

confidence: 99%

“…In a previous study (Rust et al 1998), we have been able to characterize the role of certain cis elements within the upstream promoter region of the bovine StAR gene responsible for expression in a heterologous cell system cotransfected or not with the transcription factor, steroidogenic factor-1 (SF-1; Ad4 BP; Fig. 5).…”

Section: Acute Regulation Of the Bovine Star Gene Promoter In Homologmentioning

confidence: 99%

“…Using northern and western blotting for StAR mRNA and protein, we first characterized the time-course of the acute specific stimulation of StAR gene transcription in these cell types by their natural effectors. Subsequently, we used transfection of previously characterized promoterdeletion-reporter constructs derived from the bovine StAR gene (Rust et al 1998) into cultured bovine primary ovarian theca cells to provide a completely homologous system in which to delineate elements of the StAR promoter that are required for the rapid LH-dependent increase in transcription. These results show that the time-and hormone-specificity of StAR gene transcription reside within the proximal promoter region, between 315 and the transcriptional start site.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute regulation of the bovine gene for the steroidogenic acute regulatory protein in ovarian theca and adrenocortical cells

Ivell¹,

Tillmann²,

Wang³

et al. 2000

Journal of Molecular Endocrinology

Self Cite

View full text Add to dashboard Cite

Upregulation of the steroidogenic acute regulatory protein (StAR) is implicated in the rapid synthesis and secretion of steroidogenic cells to produce steroids in response to stimulation by trophic hormones of the gonadal and stress axes. In the present study, we have assessed the kinetics of both StAR gene transcription and protein biosynthesis in primary cell cultures of bovine adrenocortical and ovarian theca cells, under conditions of acute stimulation by corticotrophin (ACTH) and luteinizing hormone (LH), respectively. In both cell systems, detectable upregulation of StAR gene transcription occurred within 1-2 h, reaching maxima at 4 h (theca cells) or 6 h (adrenocortical cells). mRNA levels returned rapidly to baseline, by 12 h or 24 h, respectively. Specific StAR protein levels were assessed by western blotting using a novel antibody raised against a bovine StAR peptide, and showed a similar fast upregulation, albeit delayed by 1-2 h compared with the mRNA. The response of the cultured theca cells was more acute than that of the adrenocortical cells, possibly reflecting the propensity of the LH receptor to desensitize rapidly, unlike the ACTH receptor. The primary bovine theca cell cultures were also used for fully homologous transfection studies using various deletion promoter-reporter constructs of the bovine StAR gene. Kinetic analysis of the results indicated that the acute transcriptional response resides within the proximal (-315 bp) promoter region, which includes two putative responsive elements for the steroidogenic factor-1. More distal promoter regions may be involved in modulating the specificity of expression by combining enhancer and inhibitory functions.

show abstract

The role of SF-1/Ad4BP in the control of the bovine gene for the steroidogenic acute regulatory (StAR) protein

Abstract: The bovine gene for the steroidogenic acute regulatory protein (StAR) was cloned and se-

Cited by 57 publications

References 33 publications

The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter

The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter

The role of the StAR protein in steroidogenesis: challenges for the future

Acute regulation of the bovine gene for the steroidogenic acute regulatory protein in ovarian theca and adrenocortical cells

Contact Info

Product

Resources

About