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Gene Review

Star  -  steroidogenic acute regulatory protein

Rattus norvegicus

Synonyms: 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


High impact information on Star


Chemical compound and disease context of Star


Biological context of Star

  • Fresh Israeli Jaffa blond (Shamouti) orange and Israeli Jaffa red Star Ruby (Sunrise) grapefruit juices affect plasma lipid metabolism and antioxidant capacity in rats fed added cholesterol [15].
  • Upon initiation of its import, C-28 StAR dissipates the inner membrane potential and causes swelling of the mitochondria [16].
  • To test this hypothesis, DAX-1 was overexpressed in the R2C cells using the Tet-on inducible gene expression system and resulted in a 45% decrease in steroid production, a 35% decrease in StAR protein, and a 39% decrease in cytochrome P450 side chain cleavage expression [17].
  • Cotransfection of the StAR promoter linked to a luciferase reporter gene and YY1 in the presence or absence of sterol regulatory element binding protein-1a (SREBP-1a) resulted in transcriptional repression [18].
  • StAR mRNA levels in cardiomyocytes were dramatically reduced after 24-h treatment with dexamethasone in a concentration-dependent manner (50% inhibitory concentration, 10 nM); maximal inhibition (to 15 +/- 6% of control; P < 0.001; n = 6) was achieved with 100 nM dexamethasone [2].

Anatomical context of Star

  • Levels of the variant of the neuronal nitric oxide synthase (nNOS) that is restricted to Leydig cells, TnNOS, significantly increased in response to ISO, CRF, and EtOH over the time course of altered StAR/PBR concentrations [19].
  • Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age [1].
  • A recombinant mutant StAR protein that cannot stimulate steroidogenesis by isolated mitochondria did not promote sterol transfer [20].
  • These observations demonstrate that StAR has sterol transfer activity, which may reflect an ability to enhance desorption of cholesterol from sterol-rich donor membranes [20].
  • The use of uncouplers and manipulation of the interior mitochondrial pH in hormone-induced ovarian granulosa cells and StAR-expressing COS cells suggests that StAR degradation is biphasic and involves two classes of proteases [16].

Associations of Star with chemical compounds

  • However, pretreatment of the rats with N(w)nitro-arginine methylester, which blocked ISO-induced increases in TnNOS, neither restored the T response to human chorionic gonadotropin nor prevented the decreases in StAR and PBR [19].
  • Results of this study confirm that SCPx mRNA levels are elevated following diabetes onset and that StAR, P450scc, and 3 beta-HSD mRNA levels do not correspond with the reduced steroid hormone profile associated with diabetes [21].
  • We suggest that the ability of StAR to promote sterol transfer explains its steroidogenic activity [20].
  • The mechanism of the effect of guanethidine to normalize hypoxia-stimulated basal corticosterone remains to be identified, although StAR protein may be an important mediator [11].
  • GnRH agonist treatment decreases progesterone synthesis, luteal peripheral benzodiazepine receptor mRNA, ligand binding and steroidogenic acute regulatory protein expression during pregnancy [22].

Regulatory relationships of Star


Other interactions of Star


Analytical, diagnostic and therapeutic context of Star


  1. Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR. Raff, H., Hong, J.J., Oaks, M.K., Widmaier, E.P. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  2. Expression and modulation of steroidogenic acute regulatory protein messenger ribonucleic acid in rat cardiocytes and after myocardial infarction. Casal, A.J., Silvestre, J.S., Delcayre, C., Capponi, A.M. Endocrinology (2003) [Pubmed]
  3. Steroidogenic acute regulatory protein in the rat brain: cellular distribution, developmental regulation and overexpression after injury. Sierra, A., Lavaque, E., Perez-Martin, M., Azcoitia, I., Hales, D.B., Garcia-Segura, L.M. Eur. J. Neurosci. (2003) [Pubmed]
  4. Steroidogenic impairment due to reduced ovarian transcription of cytochrome P450 side-chain-cleavage (P450scc) and steroidogenic acute regulatory protein (StAR) during experimental nephrotic syndrome. Peña-Rico, M., Guadalupe Ortiz-López, M., Camacho-Castillo, L., Cárdenas, M., Pedraza-Chaverri, J., Menjívar, M. Life Sci. (2006) [Pubmed]
  5. Sepsis produces depression of testosterone and steroidogenic acute regulatory (StAR) protein. Sam, A.D., Sharma, A.C., Lee, L.Y., Hales, D.B., Law, W.R., Ferguson, J.L., Bosmann, H.B. Shock (1999) [Pubmed]
  6. Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. Weber, K.S., Setchell, K.D., Stocco, D.M., Lephart, E.D. J. Endocrinol. (2001) [Pubmed]
  7. Changes in the expression of steroid metabolism-related genes in rat adrenal glands during selective REM sleep deprivation. Morita, K., Kuwada, A., Fujihara, H., Morita, Y., Sei, H. Life Sci. (2003) [Pubmed]
  8. Interaction of hormone-sensitive lipase with steroidogenic acute regulatory protein: facilitation of cholesterol transfer in adrenal. Shen, W.J., Patel, S., Natu, V., Hong, R., Wang, J., Azhar, S., Kraemer, F.B. J. Biol. Chem. (2003) [Pubmed]
  9. 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. Gambaryan, S., Butt, E., Marcus, K., Glazova, M., Palmetshofer, A., Guillon, G., Smolenski, A. J. Biol. Chem. (2003) [Pubmed]
  10. Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes. Pandak, W.M., Ren, S., Marques, D., Hall, E., Redford, K., Mallonee, D., Bohdan, P., Heuman, D., Gil, G., Hylemon, P. J. Biol. Chem. (2002) [Pubmed]
  11. Basal and adrenocorticotropin-stimulated corticosterone in the neonatal rat exposed to hypoxia from birth: modulation by chemical sympathectomy. Raff, H., Lee, J.J., Widmaier, E.P., Oaks, M.K., Engeland, W.C. Endocrinology (2004) [Pubmed]
  12. Regulation of PKC delta expression by estrogen and rat placental lactogen-1 in luteinized rat ovarian granulosa cells. Peters, C.A., Cutler, R.E., Maizels, E.T., Robertson, M.C., Shiu, R.P., Fields, P., Hunzicker-Dunn, M. Mol. Cell. Endocrinol. (2000) [Pubmed]
  13. Acute effects of ethanol on steroidogenic acute regulatory protein (StAR) in the prepubertal rat ovary. Srivastava, V.K., Hiney, J.K., Dearth, R.K., Les Dees, W. Alcohol. Clin. Exp. Res. (2001) [Pubmed]
  14. Adrenal splanchnic innervation modulates adrenal cortical responses to dehydration stress in rats. Ulrich-Lai, Y.M., Engeland, W.C. Neuroendocrinology (2002) [Pubmed]
  15. Fresh Israeli Jaffa blond (Shamouti) orange and Israeli Jaffa red Star Ruby (Sunrise) grapefruit juices affect plasma lipid metabolism and antioxidant capacity in rats fed added cholesterol. Gorinstein, S., Leontowicz, H., Leontowicz, M., Krzeminski, R., Gralak, M., Martin-Belloso, O., Delgado-Licon, E., Haruenkit, R., Katrich, E., Park, Y.S., Jung, S.T., Trakhtenberg, S. J. Agric. Food Chem. (2004) [Pubmed]
  16. Proteolysis of normal and mutated steroidogenic acute regulatory proteins in the mitochondria: the fate of unwanted proteins. Granot, Z., Geiss-Friedlander, R., Melamed-Book, N., Eimerl, S., Timberg, R., Weiss, A.M., Hales, K.H., Hales, D.B., Stocco, D.M., Orly, J. Mol. Endocrinol. (2003) [Pubmed]
  17. Regulation of steroidogenesis and steroidogenic acute regulatory protein in R2C cells by DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1). Jo, Y., Stocco, D.M. Endocrinology (2004) [Pubmed]
  18. Repression of the steroidogenic acute regulatory gene by the multifunctional transcription factor Yin Yang 1. Nackley, A.C., Shea-Eaton, W., Lopez, D., McLean, M.P. Endocrinology (2002) [Pubmed]
  19. Activation of a neural brain-testicular pathway rapidly lowers Leydig cell levels of the steroidogenic acute regulatory protein and the peripheral-type benzodiazepine receptor while increasing levels of neuronal nitric oxide synthase. Herman, M., Rivier, C. Endocrinology (2006) [Pubmed]
  20. Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein. Kallen, C.B., Billheimer, J.T., Summers, S.A., Stayrook, S.E., Lewis, M., Strauss, J.F. J. Biol. Chem. (1998) [Pubmed]
  21. Altered ovarian sterol carrier protein expression in the pregnant streptozotocin-treated diabetic rat. McLean, M.P., Warden, K.J., Sandhoff, T.W., Irby, R.B., Hales, D.B. Biol. Reprod. (1996) [Pubmed]
  22. GnRH agonist treatment decreases progesterone synthesis, luteal peripheral benzodiazepine receptor mRNA, ligand binding and steroidogenic acute regulatory protein expression during pregnancy. Sridaran, R., Philip, G.H., Li, H., Culty, M., Liu, Z., Stocco, D.M., Papadopoulos, V. J. Mol. Endocrinol. (1999) [Pubmed]
  23. Decreased expression of steroidogenic acute regulatory protein: a novel mechanism participating in the leptin-induced inhibition of glucocorticoid biosynthesis. Cherradi, N., Capponi, A.M., Gaillard, R.C., Pralong, F.P. Endocrinology (2001) [Pubmed]
  24. Interferon-gamma inhibits the steroidogenic acute regulatory protein messenger ribonucleic acid expression and protein levels in primary cultures of rat Leydig cells. Lin, T., Hu, J., Wang, D., Stocco, D.M. Endocrinology (1998) [Pubmed]
  25. Steroidogenic acute regulatory protein in ovarian follicles of gonadotropin-stimulated rats is regulated by a gonadotropin-releasing hormone agonist. Irusta, G., Parborell, F., Peluffo, M., Manna, P.R., Gonzalez-Calvar, S.I., Calandra, R., Stocco, D.M., Tesone, M. Biol. Reprod. (2003) [Pubmed]
  26. Protein phosphatase inhibitor cantharidin inhibits steroidogenesis and steroidogenic acute regulatory protein expression in cultured rat preovulatory follicles. Yu, C.C., Chen, W.Y., Li, P.S. Life Sci. (2001) [Pubmed]
  27. Expression of SR-BI receptor and StAR protein in rat ocular tissues. Provost, A.C., Péquignot, M.O., Sainton, K.M., Gadin, S., Sallé, S., Marchant, D., Hales, D.B., Abitbol, M. C. R. Biol. (2003) [Pubmed]
  28. Neurosteroids and female reproduction: estrogen increases 3beta-HSD mRNA and activity in rat hypothalamus. Soma, K.K., Sinchak, K., Lakhter, A., Schlinger, B.A., Micevych, P.E. Endocrinology (2005) [Pubmed]
  29. Autocrine regulation of steroidogenic function of Leydig cells by transforming growth factor-alpha. Millena, A.C., Reddy, S.C., Bowling, G.H., Khan, S.A. Mol. Cell. Endocrinol. (2004) [Pubmed]
  30. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Borch, J., Metzdorff, S.B., Vinggaard, A.M., Brokken, L., Dalgaard, M. Toxicology (2006) [Pubmed]
  31. Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model. Audran, M., Chappard, D., Legrand, E., Libouban, H., Baslé, M.F. Calcif. Tissue Int. (2001) [Pubmed]
  32. Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3beta-hydroxysteroid dehydrogenase in the rat brain. Furukawa, A., Miyatake, A., Ohnishi, T., Ichikawa, Y. J. Neurochem. (1998) [Pubmed]
  33. Ex vivo regulation of adrenal cortical cell steroid and protein synthesis, in response to adrenocorticotropic hormone stimulation, by the Ginkgo biloba extract EGb 761 and isolated ginkgolide B. Amri, H., Drieu, K., Papadopoulos, V. Endocrinology (1997) [Pubmed]
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