Congenital Adrenal Hyperplasia Due to a Deficiency of One of the Enzymes Involved in the Biosynthesis of Pregnenolone

Am, Camacho; Kowarski, Avinoam; Cj, Migeon; Aj, Brough

doi:10.1210/jcem-28-2-153

Cited by 81 publications

(17 citation statements)

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“…These findings have suggested that the lesion is in the first step in steroidogenesis, the conversion of cholesterol to pregnenolone. Enzymologic studies (6)(7)(8)(9) confirmed that adrenal and gonadal tissue from these patients failed to convert cholesterol to pregnenolone, consistent with the notion that the lesion is in the enzyme converting cholesterol to pregnenolone.…”

Section: Introductionsupporting

confidence: 55%

Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.

Lin¹,

Gitelman²,

Saenger³

et al. 1991

J. Clin. Invest.

116

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Congenital lipoid adrenal hyperplasia is the most severe form of congenital adrenal hyperplasia. Affected individuals can synthesize no steroid hormones, and hence are all phenotypic females with a severe salt-losing syndrome that is fatal if not treated in early infancy. All previous studies have suggested that the disorder is in the cholesterol side chain cleavage enzyme (P450scc), which converts cholesterol to pregnenolone. A newborn patient was diagnosed by the lack of significant concentrations of adrenal or gonadal steroids either before or after stimulation with corticotropin (ACTH) or gonadotropin (hCG). The P450scc gene in this patient and in a previously described patient were grossly intact, as evidenced by Southern blotting patterns. Enzymatic (polymerase chain reaction) amplification and sequencing of the coding regions of their P450scc genes showed these were identical to the previously cloned human P450scc cDNA and gene sequences. Undetected compound heterozygosity was ruled out in the new patient by sequencing P450scc cDNA enzymatically amplified from gonadal RNA. Northern blots of gonadal RNA from this patient contained normal sized mRNAs for P450scc and also for adrenodoxin reductase, adrenodoxin, sterol carrier protein 2, endozepine, and GRP-78 (the precursor to steroidogenesis activator peptide). These studies show that lipoid CAH is not caused by lesions in the P450scc gene, and suggest that another unidentified factor is required for the conversion of cholesterol to pregnenolone, and is disordered in congenital lipoid adrenal hyperplasia. (J. Clin. Invest. 1991.88:1955-1962

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Section: Introductionsupporting

confidence: 55%

Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.

Lin¹,

Gitelman²,

Saenger³

et al. 1991

J. Clin. Invest.

116

View full text Add to dashboard Cite

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“…Because these fi ndings indicate a lesion in the conversion of cholesterol to pregnenolone, lipoid CAH was initially thought to result from a disorder in an enzyme involved in this conversion; hence, before the role of P450scc was understood, lipoid CAH was mis-termed 20,22-desmolase defi ciency (246)(247)(248)(249)(250)(251). However, the CYP11A1 gene for P450scc is not mutated in these patients ( 251 ), and placental steroidogenesis persists in lipoid CAH, permitting the synthesis of the progesterone needed for term gestation; this would not be expected to happen if P450scc were involved ( 252 ).…”

Section: Disordered Star: Congenital Lipoid Adrenal Hyperplasiamentioning

confidence: 99%

Early steps in steroidogenesis: intracellular cholesterol trafficking

Miller

Bose

2011

Journal of Lipid Research

460

398

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“…The incidence of lipoid CAH is higher in people of Japanese, Korean, and Palestinian ancestry [36,46]. It has been demonstrated that mitochondria isolated from adrenals and gonads of lipoid CAH patients fail to metabolize cholesterol [253,257]. Therefore, this disease was thought to be due to an abnormality in cytochrome P450scc enzyme (CYP11A) activity that catalyzes the conversion of cholesterol to pregnenolone [258], a supposition supported by findings of mutations in the CYP11A gene in rabbits with lipoid CAH characteristics [259][260][261].…”

Section: Lipoid Congenital Adrenal Hyperplasia (Lipoid Cah) and Pathomentioning

confidence: 99%

Regulation of the Steroidogenic Acute Regulatory Protein Expression: Functional and Physiological Consequences

Manna

Stocco²

2005

curr drug targets immune endocr metabol disord

125

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Steroid hormones are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta and brain and are essential for normal reproductive function and bodily homeostasis. The rate-limiting and regulated step in steroid biosynthesis is the intramitochondrial transport of cholesterol, a process that is mediated by the steroidogenic acute regulatory (StAR) protein. The importance of StAR has been illustrated by analyses of patients with lipoid congenital adrenal hyperplasia (lipoid CAH), an autosomal recessive disorder that markedly disrupts the synthesis of all gonadal and adrenal steroids. Molecular and physio-pathological analyses have demonstrated that alterations in the StAR gene are the only known cause of lipoid CAH. Furthermore, StAR knockout mice have been generated and display a phenotype that is essentially identical to the human condition. Recent advances in tissue-specific and hormone-induced expression of the StAR protein provide insights into a number of human endocrinological health issues including developmental and reproductive abnormalities. Several factors and processes have been demonstrated to influence StAR expression in steroidogenic cells and there is increasing evidence that a transcription factor-binding site-rich region present in the proximal region of the StAR promoter is highly instrumental in StAR gene expression. In this review we focus on the significant findings that have been made with regards to the regulation of StAR expression and also on the clinical and endocrinological consequences of a non-functioning StAR gene.

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Congenital Adrenal Hyperplasia Due to a Deficiency of One of the Enzymes Involved in the Biosynthesis of Pregnenolone

Cited by 81 publications

References 0 publications

Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.

Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.

Early steps in steroidogenesis: intracellular cholesterol trafficking

Regulation of the Steroidogenic Acute Regulatory Protein Expression: Functional and Physiological Consequences

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