Corticotropin-dependent synthesis of mitochondrial proteins involved in the acute regulation of steroidogenesis

Current Opinion in Endocrinology and Diabetes

Volumn 3, Issue 3, 1996, Pages 195-201

  Stocco, Douglas M ^a   Clark, Barbara J ^b  

^a TEXAS TECH UNIVERSITY   (United States)

^b University of Louisville School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0009591146     PISSN: 10683097     EISSN: None     Source Type: Journal    
DOI: 10.1097/00060793-199606000-00002     Document Type: Article

References (58)

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28. Stocco DM, Kilgore MW: Induction of mitochondrial proteins in MA-10 Leydig tumour cells with human choriogonadotropin. Biochem J 1988, 249:95-103.
29. Stocco DM, Sodeman TC: The 30-kDa mitochondrial proteins induced by hormone stimulation in MA-10 mouse Leydig tumor cells are processed from larger precursors. J Biol Chem 1991, 266:19731-19738.
30. Stocco DM, Chen W: Presence of identical mitochondrial proteins in unstimulated constitutive steroid-producing R2C rat Leydig tumor and stimulated nonconstitutive steroid-producing MA-10 mouse Leydig tumor cells. Endocrinology 1991, 128:1918-1926.
31. Stocco DM, King S, Clark BJ: Differential effects of dimethylsulfoxide on steroidogenesis in mouse MA-10 and rat R2C Leydig tumor cells. Endocrinology 1995, 136:2993-2999.
32. Stocco DM: Further evidence that the mitochondrial proteins induced by hormone stimulation in MA-10 mouse Leydig tumor cells are involved in the acute regulation of steroidogenesis. J Steroid Biochem Mol Biol 1992, 43:319-333.
33. Stocco DM, Ascoli M: The use of genetic manipulation of MA-10 Leydig tumor cells to demonstrate the role of mitochondrial proteins in the acute regulation of steroidogenesis. Endocrinology 1993, 132:959-967.
34. Clark BJ, Wells J, King SR, Stocco DM: The purification, cloning, and expression of a novel LH-induced mitochondrial protein in MA-10 mouse Leydig tumor cells: characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem 1994, 269:28314-28322. This article is the first description of the purification, cloning, sequencing, and expression of the 30-kD protein. The expression of the cDNA for the 30-kD protein resulted in an increase in steroid synthesis in unstimulated MA-10 cells and thus the name steroidogenic acute regulatory protein or StAR was given to this protein.
35. Sugawara T, Holt JA, Driscoll D, Strauss III JF, Lin D, Miller WL, Patterson D, Clancy KP, Hart IM, Clark BJ, Stocco DM: Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the gene to 8p11.2 and a pseudogene to chromosome 13. Proc Natl Acad Sci U S A 1995, 92:4778-4782. Describes the cloning of the human homologue of the StAR protein from a human adrenal cDNA library. It also describes the expression of the StAR protein in COS-1 cells and the resultant increase in steroid synthesis in response to this expression. The chromosomal location of the StAR gene to chromosome 8 and a pseudogene to chromosome 13 is also described.
36. Clark BJ, Soo SC, Caron KM, Ikeda Y, Parker KL, Stocco DM: Hormonal and developmental regulation of the steroidogenic acute regulatory (StAR) protein. Mol Endocrinol 1995, 9:1346-1355. Characterizes the StAR mRNA and protein expression with time following hormone stimulation and compares this expression to steroid biosynthesis. It also provides a description of the structure of the mouse StAR gene and the existence of a putative SF-1 transcription site. The developmental profile of StAR mRNA expression during embryogenesis in the mouse is also described.
37. Juengel JL, Meberg BM, Turzillo AM, Nett TM, Niswender GD: Hormonal regulation of messenger ribonucleic acid encoding steroidogenic acute regulatory protein in ovine corpora lutea. Endocrinology 1995, 136:5423-5429.
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40. 2+ second messenger pathway in adrenal glomerulosa cells also results in an increase in StAR protein, which parallels the increase in aldosterone observed.
41. Pezzi V, Clark BJ, Ando S, Stocco DM, Rainey WE: Role of calmodulin-dependent protein kinase II in acute adrenal aldosterone production. J Steroid Biochem Mol Biol 1996, in press. This article utilizes a specific inhibitor of CaM kinase Il to demonstrate that inhibition of this enzyme resulted in a decrease in steroidogenesis in adrenocortical cells, as stimulated by several agents. Of greatest interest was the finding that synthesis of StAR was not inhibited by this treatment, indicating that the observed decrease in steroidogenesis was at a different locus, possibly at the delivery of cholesterol to the outer mitochondrial membrane.
42. Sugawara T, Lin D, Holt JD, Martin KO, Javitt NB, Miller WL, Strauss III JF: Structure of the human steroidogenic acute regulatory protein (StAR) gene: StAR stimulates mitochondrial cholesterol 27-hydroxylase activity. Biochemistry 1995, 34:12506-12512. Describes the structure of the human StAR gene and compares it to the human StAR pseudogene. The putative transcription sites in the StAR gene are pointed out in this study. The authors also demonstrate that StAR can successfully transfer cholesterol in COS-1 cells cotransfected with the cytochrome P450 27-hydroxylase enzyme, indicating that cytochrome P450scc is not required for cholesterol transfer.
43. Morohashi K, Honda S, Inomata Y, Handa H, Omura T: A common transacting binding factor, Ad4-binding protein, to the promoters of steroidogenic P450s. J Biol Chem 1992, 267:17913-17919.
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45. King SR, Ronen-Fuhrmann T, Timberg R, Clark BJ, Orly J, Stocco DM: Steroid production after in vitro transcription, translation, and mitochondrial processing of protein products of complementary deoxyribonucleic acid for steroidogenic acute regulatory protein. Endocrinology 1995, 136:5165-5176. Demonstrates that essentially everything that has been shown for StAR action in whole cells can be accomplished in a cell-free system. The cDNA for StAR was expressed in a cell-free system and when the incubation was performed in the presence of mitochondria, the StAR protein was imported and processed correctly. Further, addition of COS-1 cell lysate containing expressed StAR protein to isolated mitochondria resulted in a time-and dose-dependent increase in steroid production.
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49. Koizumi S, Kyoya S, Miyawaki T, Kidani H, Funabashi T, Nakashima Y, Ohta G, Itagaki E, Katagiri M: Cholesterol side-chain cleavage enzyme activity and cytochrome P450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease). Clin Chim Acta 1977, 77:301-306.
50. Hauffa PT, Miller WL, Grumbach MM, Conte FA, Kaplan SL: Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20,22-desmolase) in a patient treated for 18 years. Clin Endocrinol 1985, 23:481-493.
51. Lin D, Gitelman SE, Saenger P, Miller WL: Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia. J Clin Invest 1991, 88:1955-1962.
52. Lin D, Chang YJ, Strauss JF III, Miller WL: The human peripheral benzodiazepine receptor gene: cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia. Genomes 1993, 18:643-650.
53. Saenger P, Klonari Z, Black SM, Compagnons N, Mellon SH, Fleischer A, Abrams CAL, Shackleton CHL, Miller WL: Prenatal diagnosis of congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab 1995, 80:200-205.
54. Lin D, Sugawara T, Strauss III JF, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL: Role of steroldogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 1995, 267:1828-1831. This article is of very special interest, It illustrates that the cause of the potentially fatal disease congenital lipoid adrenal hyperplasia can be traced to nonsense mutations in the StAR gene. The etiology of this disease was previously unknown. It also demonstrated that expression of normal StAR protein was absolutely essential for the steroidogenesis.
55. Miller WL: Mitochondrial specificity of the early steps in steroidogenesis. J Steroid Biochem Mol Biol 1995, 55:607-619. In this review article Miller very nicely describes the essential role of the mitochondrial milieu in steroidogenesis. Among other things, he also summarizes the series of events that led to the characterization of StAR as the causative agent in lipoid congenital adrenal hyperplasia.
56. Tee M, Lin D, Sugaware T, Holt JA, Guiguen Y, Buckingham B, Strauss JF III, Miller WL: T-A transversion 11 bp from a splice acceptor site in the human gene for steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia. Human Mol Genet 1995, 4:2299-2305. In this article an additional mutation in SlAR that results in lipoid congenital adrenal hyperplasia is described. In the patient described, cloned genomic DNA was found to have a T to A transversion in intron 4, 11 bp from the splice acceptor site of exon 5 in the StAR gene. This transversion resulted in the finding that although most of the StAR mRNA in this patient was abnormally spliced and nonfunctional, a small percentage was, in fact, normal StAR mRNA and thus resulted in a milder form of the disease.
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