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Gene Review

STAR  -  steroidogenic acute regulatory protein

Homo sapiens

Synonyms: STARD1, START domain-containing protein 1, StAR, StARD1, Steroidogenic acute regulatory protein, mitochondrial
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Disease relevance of STAR


Psychiatry related information on STAR

  • The Logic of Argumentation (LA) offers a basis for computerized support of decision-making in the absence of numerical data, and it is being used in a project on carcinogenic risk assessment, StAR [5].
  • Measuring the effectiveness of the Star Parenting Program with parents of young children [6].
  • PRIMARY OBJECTIVE: To assess the effect of an integrated reality orientation programme (North Star Project) in acute care on the duration of post-traumatic amnesia (PTA) of patients suffering from traumatic brain injury (TBI) [7].
  • We studied the response time (RT) and reliability of three neonatal patient-triggered ventilator (PTV) systems: the Draeger Babylog 8000, the Bear Cub enhancement module (CEM), and the Infrasonics Star Sync [8].

High impact information on STAR

  • Here we show that the steroidogenic acute regulatory protein (StAR), a mitochondrial protein required for stress responses, reproduction, and sexual differentiation of male fetuses, exerts its activity transiently at the outer mitochondrial membrane rather than at its final resting place in the matrix [9].
  • Here we show that DAX-1 binds DNA and acts as a powerful transcriptional repressor of StAR gene expression, leading to a drastic decrease in steroid production [10].
  • A rising StAR: an essential role in cholesterol transport [11].
  • Liver X receptor opens a new gateway to StAR and to steroid hormones [12].
  • Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene [13].

Chemical compound and disease context of STAR

  • However, congenital lipoid adrenal hyperplasia is caused by mutations in the steroidogenic acute regulatory protein StAR; it has been thought that P450scc mutations are incompatible with human term gestation, because P450scc is needed for placental biosynthesis of progesterone, which is required to maintain pregnancy [14].
  • Mutations in StAR cause congenital lipoid adrenal hyperplasia, a cholesterol storage disorder in which synthesis of all gonadal and adrenocortical steroid hormones is severely impaired, and the cholesterol that is not efficiently moved into the mitochondria accumulates in cytoplasmic lipid droplets [15].
  • In this study, we evaluated DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzyme expressions and their correlations in epithelial ovarian carcinomas to evaluate the possible roles of these factors in regulation of intratumoral steroid metabolism and/or production [16].
  • Mutations in StAR are now shown to cause Congenital Lipoid Adrenal Hyperplasia, the last unsolved form of CAH [17].
  • Premier Platinum HpSA, as opposed to Hp StAR, cross-reacted with non-pylori Helicobacter spp. in vitro [18].

Biological context of STAR


Anatomical context of STAR

  • We examined the effects of oxysterols on the expression of steroidogenic acute regulatory protein (StAR), which increases the delivery of cholesterol to sterol-metabolizing P450s in the mitochondria [1].
  • This notion was refuted when it was discovered that sterol regulatory element binding protein-1a is a potent activator of the StAR promoter in CV-1, COS-1, and human granulosa cells [1].
  • Human granulosa and theca cells, which express endogenous SF-1, contained more than 5-fold more StAR protein following addition of 27-OHC, whereas StAR mRNA levels remained unchanged [1].
  • However, this metabolite inhibited StAR promoter activity in CV-1, COS-1 and CHO cells [1].
  • The present study was designed to explore the mechanisms of extracellular calcium (Ca2+) involved in the hCG-stimulated expression of StAR protein and steroidogenesis in a mouse Leydig tumor cell line (mLTC-1) [22].

Associations of STAR with chemical compounds

  • We previously reported that StAR mRNA levels and promoter-reporter gene activity in transiently transfected H295R human adrenocortical cells were stimulated by angiotensin II but not by K+ treatment [19].
  • Angiotensin II- and K+-stimulated aldosterone production in the adrenocortical glomerulosa cells requires induction of the steroidogenic acute regulatory protein (StAR) [19].
  • Moreover, the potent MAPK inhibitors, PD98059 and UO126, augment progesterone production in these cell cultures concomitantly with specific elevation of intracellular steroidogenic acute regulatory protein (StAR) [23].
  • Inhibition of protein synthesis by cycloheximide (CHX) drastically diminished the hCG-induced StAR protein content, indicating the requirement for on-going protein synthesis for hCG action [22].
  • Interestingly, the calcium ionophore (A23187) clearly increased (P < 0.01) StAR mRNA expression, in additive fashion with hCG [22].
  • Multiple lines of evidence show that StAR moves cholesterol from the outer to inner mitochondrial membrane, but acts exclusively on the outer membrane [24].

Physical interactions of STAR


Regulatory relationships of STAR

  • LRH-1 significantly induced StAR promoter activity in a concentration-dependent manner [20].
  • ACTH signaling antagonizes the increase in Dax-1 yet strongly activates StAR transcription [28].
  • Antiserum to StAR cross-reacts with N-218 MLN64, indicating the presence of similar epitopes in both proteins [29].
  • However, cotransfection with a steroidogenic factor-1 expression plasmid augmented both basal and forskolin-stimulated StAR promoter activity [30].

Other interactions of STAR


Analytical, diagnostic and therapeutic context of STAR

  • Elevation of StAR expression by the MAPK inhibitors involved elevation of StAR mRNA, as demonstrated by RT-PCR in the human cells [23].
  • Extracellular Ca2+ (1.5 mmol/liter) enhanced the hCG (50 microg/liter)-induced increases in StAR messenger RNA (mRNA) and protein levels (1.7 +/- 0.3-fold; 4 h), as monitored by quantitative RT-PCR and immunoblotting [22].
  • Fluorescence in situ hybridization placed the StAR locus in the region 8p11 [34].
  • Third, circular dichroism showed that cholesterol binding induced a change in StAR secondary structure [35].
  • The results of pull-down assays and mammalian two-hybrid assays confirmed interaction between N-62 StAR protein and the clone 4 translated product [26].


  1. Oxysterol regulation of steroidogenic acute regulatory protein gene expression. Structural specificity and transcriptional and posttranscriptional actions. Christenson, L.K., McAllister, J.M., Martin, K.O., Javitt, N.B., Osborne, T.F., Strauss, J.F. J. Biol. Chem. (1998) [Pubmed]
  2. Transfer of cholesterol between phospholipid vesicles mediated by the steroidogenic acute regulatory protein (StAR). Tuckey, R.C., Headlam, M.J., Bose, H.S., Miller, W.L. J. Biol. Chem. (2002) [Pubmed]
  3. Localization of the steroidogenic acute regulatory protein in human tissues. Pollack, S.E., Furth, E.E., Kallen, C.B., Arakane, F., Kiriakidou, M., Kozarsky, K.F., Strauss, J.F. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  4. Transactivation of steroidogenic acute regulatory protein in human endometriotic stromalcells is mediated by the prostaglandin EP2 receptor. Sun, H.S., Hsiao, K.Y., Hsu, C.C., Wu, M.H., Tsai, S.J. Endocrinology (2003) [Pubmed]
  5. Using new reasoning technology in chemical information systems. Judson, P.N., Fox, J., Krause, P.J. Journal of chemical information and computer sciences. (1996) [Pubmed]
  6. Measuring the effectiveness of the Star Parenting Program with parents of young children. Fox, R.A., Fox, T.A., Anderson, R.C. Psychological reports. (1991) [Pubmed]
  7. Effect of an integrated reality orientation programme in acute care on post-traumatic amnesia in patients with traumatic brain injury. De Guise, E., Leblanc, J., Feyz, M., Thomas, H., Gosselin, N. Brain injury : [BI]. (2005) [Pubmed]
  8. Response time and reliability of three neonatal patient-triggered ventilators. Bernstein, G., Cleary, J.P., Heldt, G.P., Rosas, J.F., Schellenberg, L.D., Mannino, F.L. Am. Rev. Respir. Dis. (1993) [Pubmed]
  9. Rapid regulation of steroidogenesis by mitochondrial protein import. Bose, H., Lingappa, V.R., Miller, W.L. Nature (2002) [Pubmed]
  10. DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis. Zazopoulos, E., Lalli, E., Stocco, D.M., Sassone-Corsi, P. Nature (1997) [Pubmed]
  11. A rising StAR: an essential role in cholesterol transport. Waterman, M.R. Science (1995) [Pubmed]
  12. Liver X receptor opens a new gateway to StAR and to steroid hormones. Jefcoate, C.R. J. Clin. Invest. (2006) [Pubmed]
  13. Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene. Fujieda, K., Tajima, T., Nakae, J., Sageshima, S., Tachibana, K., Suwa, S., Sugawara, T., Strauss, J.F. J. Clin. Invest. (1997) [Pubmed]
  14. Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency. Tajima, T., Fujieda, K., Kouda, N., Nakae, J., Miller, W.L. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  15. START domain proteins and the intracellular trafficking of cholesterol in steroidogenic cells. Strauss, J.F., Kishida, T., Christenson, L.K., Fujimoto, T., Hiroi, H. Mol. Cell. Endocrinol. (2003) [Pubmed]
  16. Immunolocalization of nuclear transcription factors, DAX-1 and Ad4BP/SF-1, in human common epithelial ovarian tumors: correlations with StAR and steroidogenic enzymes in epithelial ovarian carcinoma. Abd-Elaziz, M., Moriya, T., Akahira, J., Nakamura, Y., Suzuki, T., Sasano, H. Int. J. Gynecol. Pathol. (2005) [Pubmed]
  17. Mitochondrial specificity of the early steps in steroidogenesis. Miller, W.L. J. Steroid Biochem. Mol. Biol. (1995) [Pubmed]
  18. PCR-denaturing gradient gel electrophoresis and two feces antigen tests for detection of Helicobacter pylori in mice. Sjunnesson, H., Fält, T., Sturegård, E., Abu Al-Soud, W., Ljungh, A., Wadström, T. Curr. Microbiol. (2003) [Pubmed]
  19. Janus kinase 2 and calcium are required for angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription in H295R human adrenocortical cells. Li, J., Feltzer, R.E., Dawson, K.L., Hudson, E.A., Clark, B.J. J. Biol. Chem. (2003) [Pubmed]
  20. Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells. Kim, J.W., Peng, N., Rainey, W.E., Carr, B.R., Attia, G.R. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  21. Multiple steroidogenic factor 1 binding elements in the human steroidogenic acute regulatory protein gene 5'-flanking region are required for maximal promoter activity and cyclic AMP responsiveness. Sugawara, T., Kiriakidou, M., McAllister, J.M., Kallen, C.B., Strauss, J.F. Biochemistry (1997) [Pubmed]
  22. Functional assessment of the calcium messenger system in cultured mouse Leydig tumor cells: regulation of human chorionic gonadotropin-induced expression of the steroidogenic acute regulatory protein. Manna, P.R., Pakarinen, P., El-Hefnawy, T., Huhtaniemi, I.T. Endocrinology (1999) [Pubmed]
  23. Down-regulation of steroidogenic response to gonadotropins in human and rat preovulatory granulosa cells involves mitogen-activated protein kinase activation and modulation of DAX-1 and steroidogenic factor-1. Tajima, K., Dantes, A., Yao, Z., Sorokina, K., Kotsuji, F., Seger, R., Amsterdam, A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  24. StAR search--what we know about how the steroidogenic acute regulatory protein mediates mitochondrial cholesterol import. Miller, W.L. Mol. Endocrinol. (2007) [Pubmed]
  25. Steroidogenic factor 1-dependent promoter activity of the human steroidogenic acute regulatory protein (StAR) gene. Sugawara, T., Holt, J.A., Kiriakidou, M., Strauss, J.F. Biochemistry (1996) [Pubmed]
  26. Steroidogenic acute regulatory protein-binding protein cloned by a yeast two-hybrid system. Sugawara, T., Shimizu, H., Hoshi, N., Nakajima, A., Fujimoto, S. J. Biol. Chem. (2003) [Pubmed]
  27. Steroidogenic activity of StAR requires contact with mitochondrial VDAC1 and phosphate carrier protein. Bose, M., Whittal, R.M., Miller, W.L., Bose, H.S. J. Biol. Chem. (2008) [Pubmed]
  28. Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex. Gummow, B.M., Scheys, J.O., Cancelli, V.R., Hammer, G.D. Mol. Endocrinol. (2006) [Pubmed]
  29. N-218 MLN64, a protein with StAR-like steroidogenic activity, is folded and cleaved similarly to StAR. Bose, H.S., Whittal, R.M., Huang, M.C., Baldwin, M.A., Miller, W.L. Biochemistry (2000) [Pubmed]
  30. Differential activity of the cytochrome P450 17alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells. Wickenheisser, J.K., Quinn, P.G., Nelson, V.L., Legro, R.S., Strauss, J.F., McAllister, J.M. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  31. CREM confers cAMP responsiveness in human steroidogenic acute regulatory protein expression in NCI-H295R cells rather than SF-1/Ad4BP. Sugawara, T., Sakuragi, N., Minakami, H. J. Endocrinol. (2006) [Pubmed]
  32. Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women. Calvo, R.M., Asunción, M., Tellería, D., Sancho, J., San Millán, J.L., Escobar-Morreale, H.F. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  33. Orexins stimulate steroidogenic acute regulatory protein expression through multiple signaling pathways in human adrenal H295R cells. Ramanjaneya, M., Conner, A.C., Chen, J., Stanfield, P.R., Randeva, H.S. Endocrinology (2008) [Pubmed]
  34. Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13. Sugawara, T., Holt, J.A., Driscoll, D., Strauss, J.F., Lin, D., Miller, W.L., Patterson, D., Clancy, K.P., Hart, I.M., Clark, B.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  35. Steroidogenic acute regulatory protein binds cholesterol and modulates mitochondrial membrane sterol domain dynamics. Petrescu, A.D., Gallegos, A.M., Okamura, Y., Strauss, J.F., Schroeder, F. J. Biol. Chem. (2001) [Pubmed]
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