Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells.

Picado-Leonard, James; Voutilainen, Raimo; Kao, Lee-Chuan; Chung, Bon-Chu; Strauss, Jerome F.; Miller, Walter L.

doi:10.1016/s0021-9258(18)69061-1

Cited by 130 publications

(4 citation statements)

References 28 publications

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“…There are only four other known eukaryotic members of this class of enzyme: (1) P450scc, the cholesterol side-chain cleavage enzyme (Chung et al 1986;Morohashi et al 1987); (2) P450c11b, the steroid 11b-hydroxylase, and its isozyme P450c11AS, the aldosterone synthetase (Mornet et al 1989); (3) P450c24, the vitamin D 24-hydroxylase (Chen et al 1993); and (4) P450c25 (also termed "P450c27"), which catalyzes vitamin D 25-hydroxylation and the 26-or 27-hydroxylation of bile acids (Su et al 1990;Cali and Russell 1991). To promote catalysis, all of these mitochondrial P450 enzymes require electrons from NADPH that are delivered to the P450 moiety through the intermediacy of ferredoxin (Chang et al 1988;Picado-Leonard et al 1988) and ferredoxin reductase (Solish et al 1988;Lin et al 1990). The tissue distribution of expression of these P450s is highly specific, but ferredoxin (Picado-Leonard et al 1988) and ferredoxin reductase (Brentano et al 1992) are found in all human tissues examined, albeit in highly varying quantities; thus, there may be other mitochondrial P450 enzymes that remain to be characterized.…”

Section: Discussionmentioning

confidence: 99%

“…To promote catalysis, all of these mitochondrial P450 enzymes require electrons from NADPH that are delivered to the P450 moiety through the intermediacy of ferredoxin (Chang et al 1988;Picado-Leonard et al 1988) and ferredoxin reductase (Solish et al 1988;Lin et al 1990). The tissue distribution of expression of these P450s is highly specific, but ferredoxin (Picado-Leonard et al 1988) and ferredoxin reductase (Brentano et al 1992) are found in all human tissues examined, albeit in highly varying quantities; thus, there may be other mitochondrial P450 enzymes that remain to be characterized. It may be noteworthy that all mitochondrial P450 enzymes characterized to date catalyze biosynthetic processes, in contrast to the many hepatic microsomal (class II) P450 enzymes, which are primarily involved in the catabolism of xenobiotics.…”

Section: Discussionmentioning

confidence: 99%

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Genetics of Vitamin D 1α-Hydroxylase Deficiency in 17 Families

Wang

Lin

Burridge

et al. 1998

The American Journal of Human Genetics

187

124

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Vitamin D-dependent rickets type I (VDDR-I), also known as pseudo-vitamin D-deficiency rickets, appears to result from deficiency of renal vitamin D 1alpha-hydroxylase activity. Prior work has shown that the affected gene lies on 12q13.3. We recently cloned the cDNA and gene for this enzyme, mitochondrial P450c1alpha, and we and others have found mutations in its gene in a few patients. To determine whether all patients with VDDR-I have mutations in P450c1alpha, we have analyzed the P450c1alpha gene in 19 individuals from 17 families representing various ethnic groups. The whole gene was PCR amplified and subjected to direct sequencing; candidate mutations were confirmed by repeat PCR of the relevant exon from genomic DNA from the patients and their parents. Microsatellite haplotyping with the markers D12S90, D12S305, and D12S104 was also done in all families. All patients had P450c1alpha mutations on both alleles. In the French Canadian population, among whom VDDR-I is common, 9 of 10 alleles bore the haplotype 4-7-1 and carried the mutation 958DeltaG. This haplotype and mutation were also seen in two other families and are easily identified because the mutation ablates a TaiI/MaeII site. Six families of widely divergent ethnic backgrounds carried a 7-bp duplication in association with four different microsatellite haplotypes, indicating a mutational hot spot. We found 14 different mutations, including 7 amino acid replacement mutations. When these missense mutations were analyzed by expressing the mutant enzyme in mouse Leydig MA-10 cells and assaying 1alpha-hydroxylase activity, none retained detectable 1alpha-hydroxylase activity. These studies show that most if not all patients with VDDR-I have severe mutations in P450c1alpha, and hence the disease should be referred to as "1alpha-hydroxylase deficiency."

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetics of Vitamin D 1α-Hydroxylase Deficiency in 17 Families

Wang

Lin

Burridge

et al. 1998

The American Journal of Human Genetics

187

124

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“…Regulation of CYP11A1 mRNA in the Placenta. Analogues of cAMP stimulate CYP11A1 mRNA and progesterone accumulation in primary cultures of human placental tissue and differentiating cytotrophoblasts (259)(260)(261) and human choriocarcinoma JEG-3 (262,263) and BeWo cells (264,265). The extracellular factors that propagate cAMP signals in placental cells in vivo, however, remain to be discovered.…”

Section: Hormonal Control Of Cyp11a1 Gene Expressionmentioning

confidence: 99%

Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B

LaVoie

King

2009

Exp Biol Med (Maywood)

218

159

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Expression of the genes that mediate the first steps in steroidogenesis, the steroidogenic acute regulatory protein (STARD1), the cholesterol side-chain cleavage enzyme, cytochrome P450scc (CYP11A1) and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (HSD3B), is tightly controlled by a battery of transcription factors in the adrenal cortex, the gonads and the placenta. These genes generally respond to the same hormones that stimulate steroid production through common pathways such as cAMP signaling and common actions on their promoters by proteins such as NR5A and GATA family members. However, there are distinct temporal, tissue and species-specific differences in expression between the genes that are defined by combinatorial regulation and unique promoter elements. This review will provide an overview of the hormonal and transcriptional regulation of the STARD1, CYP11A1 and specific steroidogenic HSD3B genes in the adrenal, testis, ovary and placenta and discuss the current knowledge regarding the key transcriptional factors involved.

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“…30) In 1986, the laboratory of Afanasii A. Akhrem in Moscow showed that the amino acid sequences of bovine adrenal 'adrenodoxin' and liver 'hepatoredoxin' were identical, 31) suggesting there was only one mammalian ferredoxin. Bovine adrenodoxin cDNA was cloned in 1985 32) ; human adrenal adrenodoxin 33) and placental ferredoxin 34) cDNAs were cloned in 1988, revealing identical sequences, showing that the same gene was expressed in both tissues; thus, finding a single gene for adrenodoxin 35) was the expected result. The single FDX1 gene is located on chromosome 11q22, with nonexpressed pseudogenes on 20q11-q12, 36,37) and is predominantly, but not exclusively, expressed in steroidogenic tissues.…”

Section: Ferredoxinsmentioning

confidence: 98%

Steroidogenic electron-transfer factors and their diseases

Miller

2021

Ann Pediatr Endocrinol Metab

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Most steroidogenesis disorders are caused by mutations in genes encoding the steroidogenic enzymes, but work in the past 20 years has identified related disorders caused by mutations in the genes encoding the cofactors that transport electrons from NADPH to P450 enzymes. Most P450s are microsomal and require electron donation by P450 oxidoreductase (POR); by contrast, mitochondrial P450s require electron donation via ferredoxin reductase (FdxR) and ferredoxin (Fdx). POR deficiency is the most common and best-described of these new forms of congenital adrenal hyperplasia. Severe POR deficiency is characterized by the Antley-Bixler skeletal malformation syndrome and genital ambiguity in both sexes, and hence is easily recognized, but mild forms may present only with infertility and subtle disorders of steroidogenesis. The common POR polymorphism A503V reduces catalysis by P450c17 (17-hydroxylase/17,20-lyase) and the principal drugmetabolizing P450 enzymes. The 17,20-lyase activity of P450c17 requires the allosteric action of cytochrome b5, which promotes interaction of P450c17 with POR, with consequent electron transfer. Rare b5 mutations are one of several causes of 17,20-lyase deficiency. In addition to their roles with steroidogenic mitochondrial P450s, Fdx and FdxR participate in the synthesis of iron-sulfur clusters used by many enzymes. Disruptions in the assembly of Fe-S clusters is associated with Friedreich ataxia and Parkinson disease. Recent work has identified mutations in FdxR in patients with neuropathic hearing loss and visual impairment, somewhat resembling the global neurologic disorders seen with mitochondrial diseases. Impaired steroidogenesis is to be expected in such individuals, but this has not yet been studied.

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Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells.

Cited by 130 publications

References 28 publications

Genetics of Vitamin D 1α-Hydroxylase Deficiency in 17 Families

Genetics of Vitamin D 1α-Hydroxylase Deficiency in 17 Families

Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B

Steroidogenic electron-transfer factors and their diseases

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