Disease relevance of Star

• These findings may impact future treatment strategies aimed at reducing androgen; for example, in the treatment of prostatic cancer, antiandrogen treatment might benefit from adjuvant therapy to inhibit StAR expression [1].
• To allow us to explore the roles of StAR in a system amenable to experimental manipulation and to develop an animal model for the human disorder lipoid congenital adrenal hyperplasia (lipoid CAH), we used targeted gene disruption to produce StAR knockout mice [2].
• Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia [2].
• The fusion proteins GST-SAG1/2, GST-SAG1 and GST-SAG2 were expressed in BL21 Star (DE3) Escherichia coli and purified by GSTrap FF columns [3].
• It is also sensitive to induction of cleft palate by glucocorticoids, as are its A strain relatives. "Star" strain is free of spontaneous clefts, and is resistant to glucocorticoid teratogenic effects [4].

High impact information on Star

• Liver X receptor opens a new gateway to StAR and to steroid hormones [5].
• Basally, Lxralphabeta-/- mice exhibited a marked decrease in ABCA1 and a derepression of StAR expression, causing a net decrease in cholesterol efflux and an increase in steroidogenesis [6].
• Glucocorticoid synthesis requires intramitochondrial cholesterol transport mediated by the steroidogenic acute regulatory protein (StAR) [5].
• However, compensatory mechanisms, such as cellular hypertrophy and increased expression of the rate-limiting steroidogenic protein StAR, help to maintain adrenal function at near normal capacity under basal conditions [7].
• Histologically, the adrenal cortex of StAR knockout mice contained florid lipid deposits, with lesser deposits in the steroidogenic compartment of the testis and none in the ovary [2].

Chemical compound and disease context of Star

• StAR mutations in humans cause congenital lipoid adrenal hyperplasia (lipoid CAH), an autosomal recessive condition with severe deficiencies of all classes of steroid hormones [8].

Biological context of Star

• The open reading frame sequence differed at only 12 amino acids from that of the mouse Star [9].
• The rat Star gene seven exons with exon 7 encoding the entire 2.5 kb of 3'-UTR of the 3.5-kb mRNA [9].
• A 3.5-kb Star cDNA clone isolated from a rat adrenal cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3'-untranslated region (3'-UTR) [9].
• We observed significant downregulation of Cyp19a1 and upregulation of Star and Cyp11a1 mRNA expression in both COCs and MGCs after in vivo administration of hCG or in vitro treatment with gonadotropins or 8-Br-cAMP [10].
• These studies provide novel insights into the mechanisms that regulate StAR gene expression and extend our understanding of SF-1's global roles within steroidogenic cells [11].

Anatomical context of Star

• Molecular mechanisms of insulin-like growth factor-I mediated regulation of the steroidogenic acute regulatory protein in mouse leydig cells [12].
• Mitochondria isolated from cells treated with ODNs antisense, but not missense, to PBR failed to form pregnenolone and respond to either StAR or Tom/StAR proteins [13].
• The steroidogenic acute regulatory (StAR) protein mediates the rate-limiting step of steroidogenesis, which is the transfer of cholesterol to the inner mitochondrial membrane [14].
• Furthermore, we have demonstrated that these two C/EBP binding sites are required for steroidogenic factor-1 (SF-1)-dependent transactivation of the StAR promoter in a nonsteroidogenic cell line [14].
• Histological abnormalities of the testes were seen from early developmental stages and were associated with markedly decreased Leydig cell expression of two essential components of testosterone biosynthesis, Cyp11a and the steroidogenic acute regulatory protein [15].

Associations of Star with chemical compounds

• The steroidogenic acute regulatory protein (StAR) is essential for the regulated production of steroid hormones, mediating the translocation of intracellular cholesterol to the inner mitochondrial membrane where steroidogenesis begins [16].
• These findings extend our understanding of steroidogenic cell dysfunction in StAR KO mice and highlight key roles of trophic hormones and high-density lipoprotein-derived cholesterol in lipid deposits within StAR-deficient steroidogenic cells [16].
• Through sequence analysis, deoxyribonuclease I (DNAse I) footprinting and electrophoretic mobility shift assays (EMSAs), we have identified two putative CCAAT/enhancer binding protein (C/EBP) DNA elements at -113 (C1) and -87 (C2) in the mouse StAR promoter [14].
• T(3) acutely (8 h), induced a 260% increase in StAR messenger RNA (mRNA) expression over the basal level which was coincident with an increase in progesterone (P) production [17].
• Androgen-mediated inhibition of StAR expression was also observed in primary Leydig cell culture and in vivo using both hypophysectomized mice and mice treated with the GnRH antagonist, acyline [1].
• In these cells, small interfering RNA-mediated NUR77 knockdown reduces cAMP-induced StAR expression [18].

Physical interactions of Star

• In vivo chromatin immunoprecipitation assays demonstrated CREB binding to the StAR proximal promoter is independent of (Bu)2cAMP-treatment, confirming our in vitro analysis [19].
• Steroidogenic acute regulatory protein binds cholesterol and modulates mitochondrial membrane sterol domain dynamics [20].
• Phosphatidylcholine transfer protein (PC-TP) is a cytosolic phospholipid binding protein and a member of the steroidogenic acute regulatory-related transfer domain superfamily [21].

Co-localisations of Star

• P450scc mRNA colocalized in all sites where StAR mRNA was found, and in bovine liver [22].

Regulatory relationships of Star

• Conversely, StAR gene transcription was markedly inhibited by expression of nonphosphorylatable CREB (Ser(133)Ala), dominant negative A-CREB, and dominant negative c-Jun (TAM-67) mutants [12].
• Inhibition of cyclooxygenase-2 activity enhances steroidogenesis and steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells [23].
• We hypothesized that the MIS-induced StAR expression is the indirect result of reduced testosterone synthesis in Leydig cells caused by MIS [1].
• Corticotropin-releasing hormone stimulates the expression of the steroidogenic acute regulatory protein in MA-10 mouse cells [24].
• SR-BI mRNA and protein were expressed at high levels in the adrenal glands of knockout mice lacking the steroidogenic acute regulatory protein; these mice have extensive lipid deposits in the adrenocortical cells and high circulating levels of ACTH [25].
• Cotransfection of TIS11b selectively decreases cytomegalovirus-promoted Star mRNA and luciferase-Star 3'-UTR reporters harboring the extended 3'-UTR [26].

Other interactions of Star

• MA-10 mouse Leydig tumor cells were treated with and without oligodeoxynucleotides (ODNs) antisense to PBR and StAR followed by treatment with saturating concentrations of human choriogonadotropin [13].
• Lipid accumulation was ameliorated considerably in StAR KO/hpg mice but was restored by treatment with exogenous gonadotropins, directly linking trophic hormones with gonadal lipid accumulation [16].
• In the ovary, all three ERKOs exhibited normal expression of Star, Cyp11a, and Hsd3b1 [27].
• In addition, (Bu)2cAMP-treatment increased phosphorylated CREB (P-CREB) association with the StAR promoter but did not influence total CREB interaction [19].
• The induction of steroidogenic acute regulatory protein (StAR) mRNA by cAMP, however, was slightly increased by addition of MIS [28].

Analytical, diagnostic and therapeutic context of Star

• Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold [9].
• The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner [29].
• Also, HPLC was used to identify AA metabolites involved in StAR gene transcription [30].
• Expression of steroidogenic acute regulatory protein (StAR) was monitored by real-time PCR and Western blotting [31].
• To determine the sequence elements required for hormone inducibility of the StAR promoter, truncated regions of the -1002/+6 sequence of the mouse gene were ligated to pCAT-Basic plasmid and transfected by electroporation to freshly prepared cells [32].

References