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Gene Review

Star  -  steroidogenic acute regulatory protein

Mus musculus

Synonyms: AV363654, D8Ertd419e, Luteinizing hormone-induced protein, START domain-containing protein 1, StAR, ...
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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


Anatomical context of Star


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


Co-localisations of Star

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

Regulatory relationships of Star


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


  1. Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens. Houk, C.P., Pearson, E.J., Martinelle, N., Donahoe, P.K., Teixeira, J. Endocrinology (2004) [Pubmed]
  2. Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. Caron, K.M., Soo, S.C., Wetsel, W.C., Stocco, D.M., Clark, B.J., Parker, K.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Protective immunity against Toxoplasma gondii in mice induced by a chimeric protein rSAG1/2. Yang, C.D., Chang, G.N., Chao, D. Parasitol. Res. (2004) [Pubmed]
  4. Genetic variation in spontaneous and diphenylhydantoin-induced craniofacial malformations in mice. Brown, K.S., Evans, M.I., Harne, L.C. Journal of craniofacial genetics and developmental biology. Supplement. (1985) [Pubmed]
  5. Liver X receptor opens a new gateway to StAR and to steroid hormones. Jefcoate, C.R. J. Clin. Invest. (2006) [Pubmed]
  6. Liver X receptors regulate adrenal cholesterol balance. Cummins, C.L., Volle, D.H., Zhang, Y., McDonald, J.G., Sion, B., Lefrançois-Martinez, A.M., Caira, F., Veyssière, G., Mangelsdorf, D.J., Lobaccaro, J.M. J. Clin. Invest. (2006) [Pubmed]
  7. Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response. Bland, M.L., Jamieson, C.A., Akana, S.F., Bornstein, S.R., Eisenhofer, G., Dallman, M.F., Ingraham, H.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Developmental roles of the steroidogenic acute regulatory protein (StAR) as revealed by StAR knockout mice. Hasegawa, T., Zhao, L., Caron, K.M., Majdic, G., Suzuki, T., Shizawa, S., Sasano, H., Parker, K.L. Mol. Endocrinol. (2000) [Pubmed]
  9. Characterization of the rat Star gene that encodes the predominant 3.5-kilobase pair mRNA. ACTH stimulation of adrenal steroids in vivo precedes elevation of Star mRNA and protein. Ariyoshi, N., Kim, Y.C., Artemenko, I., Bhattacharyya, K.K., Jefcoate, C.R. J. Biol. Chem. (1998) [Pubmed]
  10. Participation of mitogen-activated protein kinase in luteinizing hormone-induced differential regulation of steroidogenesis and steroidogenic gene expression in mural and cumulus granulosa cells of mouse preovulatory follicles. Su, Y.Q., Nyegaard, M., Overgaard, M.T., Qiao, J., Giudice, L.C. Biol. Reprod. (2006) [Pubmed]
  11. Characterization of the promoter region of the mouse gene encoding the steroidogenic acute regulatory protein. Caron, K.M., Ikeda, Y., Soo, S.C., Stocco, D.M., Parker, K.L., Clark, B.J. Mol. Endocrinol. (1997) [Pubmed]
  12. Molecular mechanisms of insulin-like growth factor-I mediated regulation of the steroidogenic acute regulatory protein in mouse leydig cells. Manna, P.R., Chandrala, S.P., King, S.R., Jo, Y., Counis, R., Huhtaniemi, I.T., Stocco, D.M. Mol. Endocrinol. (2006) [Pubmed]
  13. Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into leydig cell mitochondria. Hauet, T., Yao, Z.X., Bose, H.S., Wall, C.T., Han, Z., Li, W., Hales, D.B., Miller, W.L., Culty, M., Papadopoulos, V. Mol. Endocrinol. (2005) [Pubmed]
  14. SF-1 (steroidogenic factor-1) and C/EBP beta (CCAAT/enhancer binding protein-beta) cooperate to regulate the murine StAR (steroidogenic acute regulatory) promoter. Reinhart, A.J., Williams, S.C., Clark, B.J., Stocco, D.M. Mol. Endocrinol. (1999) [Pubmed]
  15. Cell-specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Jeyasuria, P., Ikeda, Y., Jamin, S.P., Zhao, L., De Rooij, D.G., Themmen, A.P., Behringer, R.R., Parker, K.L. Mol. Endocrinol. (2004) [Pubmed]
  16. The roles of circulating high-density lipoproteins and trophic hormones in the phenotype of knockout mice lacking the steroidogenic acute regulatory protein. Ishii, T., Hasegawa, T., Pai, C.I., Yvgi-Ohana, N., Timberg, R., Zhao, L., Majdic, G., Chung, B.C., Orly, J., Parker, K.L. Mol. Endocrinol. (2002) [Pubmed]
  17. Assessment of mechanisms of thyroid hormone action in mouse Leydig cells: regulation of the steroidogenic acute regulatory protein, steroidogenesis, and luteinizing hormone receptor function. Manna, P.R., Kero, J., Tena-Sempere, M., Pakarinen, P., Stocco, D.M., Huhtaniemi, I.T. Endocrinology (2001) [Pubmed]
  18. The orphan nuclear receptor NUR77 regulates hormone-induced StAR transcription in Leydig cells through cooperation with Ca2+/calmodulin-dependent protein kinase I. Martin, L.J., Boucher, N., Brousseau, C., Tremblay, J.J. Mol. Endocrinol. (2008) [Pubmed]
  19. Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter. Clem, B.F., Hudson, E.A., Clark, B.J. Endocrinology (2005) [Pubmed]
  20. 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]
  21. Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice. Wang, W.J., Baez, J.M., Maurer, R., Dansky, H.M., Cohen, D.E. J. Lipid Res. (2006) [Pubmed]
  22. Steroidogenic acute regulatory protein in bovine corpora lutea. Pescador, N., Soumano, K., Stocco, D.M., Price, C.A., Murphy, B.D. Biol. Reprod. (1996) [Pubmed]
  23. Inhibition of cyclooxygenase-2 activity enhances steroidogenesis and steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells. Wang, X., Dyson, M.T., Jo, Y., Stocco, D.M. Endocrinology (2003) [Pubmed]
  24. Corticotropin-releasing hormone stimulates the expression of the steroidogenic acute regulatory protein in MA-10 mouse cells. Huang, B.M., Stocco, D.M., Li, P.H., Yang, H.Y., Wu, C.M., Norman, R.L. Biol. Reprod. (1997) [Pubmed]
  25. Developmental and hormonal regulation of murine scavenger receptor, class B, type 1. Cao, G., Zhao, L., Stangl, H., Hasegawa, T., Richardson, J.A., Parker, K.L., Hobbs, H.H. Mol. Endocrinol. (1999) [Pubmed]
  26. cAMP-dependent posttranscriptional regulation of steroidogenic acute regulatory (STAR) protein by the zinc finger protein ZFP36L1/TIS11b. Duan, H., Cherradi, N., Feige, J.J., Jefcoate, C. Mol. Endocrinol. (2009) [Pubmed]
  27. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Couse, J.F., Yates, M.M., Walker, V.R., Korach, K.S. Mol. Endocrinol. (2003) [Pubmed]
  28. Müllerian inhibiting substance blocks the protein kinase A-induced expression of cytochrome p450 17alpha-hydroxylase/C(17-20) lyase mRNA in a mouse Leydig cell line independent of cAMP responsive element binding protein phosphorylation. Laurich, V.M., Trbovich, A.M., O'Neill, F.H., Houk, C.P., Sluss, P.M., Payne, A.H., Donahoe, P.K., Teixeira, J. Endocrinology (2002) [Pubmed]
  29. Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein. Hales, K.H., Diemer, T., Ginde, S., Shankar, B.K., Roberts, M., Bosmann, H.B., Hales, D.B. Endocrinology (2000) [Pubmed]
  30. Involvement of 5-lipoxygenase metabolites of arachidonic acid in cyclic AMP-stimulated steroidogenesis and steroidogenic acute regulatory protein gene expression. Wang, X.J., Dyson, M.T., Jo, Y., Eubank, D.W., Stocco, D.M. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  31. Low concentrations mono-butyl phthalate stimulates steroidogenesis by facilitating steroidogenic acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1). Wang, Y., Song, L., Hong, X., Cui, L., Zhang, Z., Xiao, H., Zhou, J., Wang, X. Chem. Biol. Interact. (2006) [Pubmed]
  32. CCAAT enhancer-binding protein beta and GATA-4 binding regions within the promoter of the steroidogenic acute regulatory protein (StAR) gene are required for transcription in rat ovarian cells. Silverman, E., Eimerl, S., Orly, J. J. Biol. Chem. (1999) [Pubmed]
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