Control of cholesterol access to cytochrome P450scc in rat adrenal cells mediated by regulation of the steroidogenic acute regulatory protein

Kim, Young Cheul; Ariyoshi, Noritaka; Artemenko, Irina; Elliott, Mary; Bhattacharyya, K K; Jefcoate, Colin R.

doi:10.1016/s0039-128x(96)00153-5

Cited by 41 publications

(26 citation statements)

References 64 publications

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“…Although ACTH increased the intensity of the three mRNA bands (1·7, 3·1 and 5·3 kb), the 1·7 and 3·1 kb mRNA bands were the most affected. In agreement with our results, Kim et al (1997) reported that in hypophysectomised rats, ACTH stimulated 1·6 and 3·5 kb mRNA levels in whole adrenals.…”

Section: Discussionsupporting

confidence: 94%

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In vivo effects of adrenocorticotrophin on the expression of the hamster steroidogenic acute regulatory protein

Fleury

Ducharme²,

LeHoux³

1998

Journal of Molecular Endocrinology

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In this study, we report the cDNA cloning of hamster adrenal steroidogenic acute regulatory (StAR) protein and the effect of adrenocorticotrophin (ACTH) on its expression in vivo. A hamster adrenal cDNA library was screened using an 852 bp fragment obtained by polymerase chain reaction; this fragment corresponds to the entire coding sequence (CDS) of the hamster adrenal StAR cDNA. Ten clones of different lengths were isolated and sequenced. The longest clone was 1564 bp and contained 34 bp in the 5 -untranslated region, 852 bp in the CDS, and 678 bp in the 3 -untranslated region (3 -UTR). Two polyadenylation signal sequences were found in the 3 -UTR. The CDS of the ten isolated clones was identical, but six of these lacked the last 132 nucleotides in the 3 -UTR, thus indicating that they had used the first polyadenylation signal. The hamster StAR protein contains 284 amino acid residues, and is 91·9% homologous to mouse, 90·5% to rat, 86·4% to human, 85% to porcine, and 82·5% to bovine StAR protein. Southern blot analysis indicated the presence of only one StAR gene in the hamster genome. Northern blotting analysis revealed the presence of the StAR mRNA in male and female steroidogenic tissues, namely adrenals and gonads, but not in the liver or in the kidneys of either sex. Three mRNA species of 1·7, 3·1 and 5·3 kb were found in whole hamster adrenals. Administration of ACTH to hamsters provoked increases (two-to threefold) in the adrenal content of the StAR mRNA within 1 h in vivo. Western blotting analysis on adrenal mitochondria showed that the level of StAR protein was also significantly elevated (1·5-fold) 1 h after ACTH treatment.

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Section: Discussionsupporting

confidence: 94%

“…In agreement with this hypothesis, Hartung et al (1995) have cloned a bovine StAR transcript from a downstream polyadenylation site which gives rise to a long 3 -UTR. In the rat, the very long exon seven explains the synthesis of the 3·5 kb mRNA (Kim et al 1997). Longer mRNA species could also come from alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

In vivo effects of adrenocorticotrophin on the expression of the hamster steroidogenic acute regulatory protein

Fleury

Ducharme²,

LeHoux³

1998

Journal of Molecular Endocrinology

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“…Under such conditions, the levels of StAR mRNA were significantly elevated in the ZG (210 -270%) and ZFR (450 -870%), and the levels of StAR protein (expressed on a milligram of protein basis) were also significantly elevated in the ZG (150%) and ZFR (160%), indicating the importance of StAR protein in maintaining a high level of steroidogenesis in a situation similar to that which prevails in Cushing's syndrome. In agreement with our results, ACTH administration to hypophysectomized rats resulted in an increase in adrenal StAR mRNA 24 h after treatment (40). In H295R adrenocortical cells, (Bu) 2 cAMP induced StAR protein expression (41).…”

Section: Figsupporting

confidence: 92%

The Acute and Chronic Effects of Adrenocorticotropin on the Levels of Messenger Ribonucleic Acid and Protein of Steroidogenic Enzymes in Rat Adrenal in Vivo*

1998

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The purpose of this study was to evaluate the effects of acute (a single injection) and chronic stimulation (twice daily injection for 9 days) by ACTH on changes occurring in the temporal expression of steroidogenic enzymes in the rat adrenal in vivo. Under acute ACTH stimulation, the level of steroidogenic acute regulatory protein (StAR) messenger RNA (mRNA) was increased within 0.5 h in both zona glomerulosa (ZG) and zona fasciculata-reticularis (ZFR), with maximal increases of 220 -370% and 300 -350% in the ZG and ZFR, respectively. Increases in the levels of StAR protein in homogenates were also found in the ZG (700%) and the ZFR (300%), but were delayed compared with those of their mRNA. Furthermore, the increase in mitochondrial StAR protein was concomitant with that in the homogenate, indicating that the entry of StAR into mitochondria might not be necessary to increase steroidogenesis during the early stimulatory phase. The levels of c-jun, c-fos, junB, and fosB mRNA in ZG and ZFR were also rapidly maximally elevated within 0.5-1 h after ACTH administration and fell to near control levels 5 h posttreatment. The levels of c-jun protein were already increased in both zones at 1 h, reached 200% at 3 h, and remained elevated 5 h post-ACTH treatment. The levels of c-Fos protein were maximally increased by 240% in both zones after 1 h and decreased thereafter to control values at 5 h. Few changes were observed in the adrenal protein contents of cholesterol side-chain cleavage cytochrome P450 (P450scc), cytochrome P450 11␤-hydroxylase (P450C11), cytochrome P450 21-hydroxylase (P450C21), and 3␤-hydroxysteroid dehydrogenase (3␤HSD). Under chronic stimulation by ACTH, we observed elevations in the levels of plasma corticosteroids and changes in the mRNA and protein levels of many adrenal steroidogenic enzymes in both zones. In the ZG, administration of ACTH for 9 days provoked an increase in the level of StAR mRNA (210 -270%) and a decrease in the levels of 3␤HSD, cytochrome P450 aldosterone synthase (P450aldo), and AT 1 receptor mRNA (by 40%, 70%, and 90%, respectively), whereas the levels of P450scc and P450C21 mRNA did not differ significantly from the control values. Western blotting analysis showed that the adrenal ZG protein levels of StAR and P450scc were increased (150%), 3␤HSD was not changed, and P450C21 was decreased by 70%. In the ZFR, the levels of P450scc and StAR mRNAs were increased (260% and 570 -870%, respectively). The levels of 3␤HSD, P450C21, and P450C11 mRNA did not differ from control values in that zone. Western blotting analysis showed that the ZFR protein level of 3␤HSD was not changed, P450scc and P450C21 were decreased by 40% and 60%, respectively, and StAR was increased by 160%. Although c-fos and fosB mRNAs were undetectable after 9 days of chronic ACTH treatment, c-jun mRNA and its protein were still detectable, suggesting a basic role for this protooncogene in maintaining the integrity and function of the adrenal cortex. When dexamethasone was administered to rats for 5 days...

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“…This is also seen in all other sources of Star expression (1.6 and 3.4 kb (mouse MA-10 cells) (26), 1.8 and 3.0 kb (bovine luteal cells) (16), 1.6 and 2.8 kb (ovine luteal cells) (15), and 1.6 and 4.4 kb (human) (21)). However, unlike MA-10 cells, the rat adrenal in vivo expresses the 3.5-kb mRNA as the predominant form (42). We have shown that this 3.5-kb mRNA arises from a 1.9-kb extension of the 1.6-kb species in the 3Ј-UTR region which is encoded by a continuation of exon 7 of the Star gene.…”

Section: Table I Primers Used For the Generation Of Pcr Productsmentioning

confidence: 86%

Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

Ariyoshi¹,

Kim²,

Artemenko

et al. 1998

Journal of Biological Chemistry

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The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3.5-kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating (ϳ85% of total) in vivo. 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.

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Control of cholesterol access to cytochrome P450scc in rat adrenal cells mediated by regulation of the steroidogenic acute regulatory protein

Cited by 41 publications

References 64 publications

In vivo effects of adrenocorticotrophin on the expression of the hamster steroidogenic acute regulatory protein

In vivo effects of adrenocorticotrophin on the expression of the hamster steroidogenic acute regulatory protein

The Acute and Chronic Effects of Adrenocorticotropin on the Levels of Messenger Ribonucleic Acid and Protein of Steroidogenic Enzymes in Rat Adrenal in Vivo*

Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

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