Multiple gene-like sequences related to the rabbit hepatic progesterone 21-hydroxylase cytochrome P-450 1.

Tukey, Robert H.; Okino, Steve T.; Barnes, Henry J.; Griffin, Keith J.; Johnson, Eric F.

doi:10.1016/s0021-9258(17)38876-2

Cited by 83 publications

(17 citation statements)

References 44 publications

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“…The cDNAs can be grouped into two closely related categories, the MP-4/MP-8 and the MP-12/MP-20 types. Computer analysis had previously shown (Umbenhauer et al, 1987b) that the MP-8 sequence shares 80% similarity with that of a rabbit liver progesterone 21-hydroxylase P-450 1 cDNA (Tukey et al, 1985). The same degree of identity was observed between MP-12/MP-20 and rabbit P-450 1 clones (Tukey et al, 1985).…”

Section: Resultsmentioning

confidence: 62%

“…Computer analysis had previously shown (Umbenhauer et al, 1987b) that the MP-8 sequence shares 80% similarity with that of a rabbit liver progesterone 21-hydroxylase P-450 1 cDNA (Tukey et al, 1985). The same degree of identity was observed between MP-12/MP-20 and rabbit P-450 1 clones (Tukey et al, 1985). Yoshioka et al (1987) have also characterized a rat cDNA clone highly similar (71%) to MP-8, and this cDNA appears to code for a constitutive male-specific P-450 protein (P-450M1).…”

Section: Resultsmentioning

confidence: 99%

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Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase

et al. 1988

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A cytochrome P-450 (P-450) multigene family codes for several related human liver enzymes, including the P-450 responsible for (S)-mephenytoin 4'-hydroxylation. This enzyme activity has previously been shown to be associated with a genetic polymorphism. Genomic (Southern) blot analysis using non-overlapping 5' and 3' portions of a cDNA clone suggests that approximately seven related sequences are present in this gene family. In this study four cDNA clones, all nearly full-length, were isolated from a bacteriophage lambda gt11 library prepared from a single human liver. These clones can be grouped into two categories that are approximately 85% identical at the level of DNA sequence. The cDNA clones in one category (MP-4, MP-8) both match the N-terminal sequences of the P-450MP-1 and P-450MP-2 proteins, which had previously been shown to be catalytically active in (S)-mephenytoin 4'-hydroxylation. These two cDNAs, MP-4 and MP-8, differ in only two bases in the coding region but are quite distinct in their 3' noncoding regions. Another protein (P-450MP-3) was isolated on the basis of its immunochemical similarity to P-450MP-1 but was found to be catalytically inactive; amino acid sequencing of tryptic peptides of P-450MP-3 showed a correspondence to the second category of cDNA clones (MP-12, MP-20), which differ from each other in only four (nonsilent) base changes. Oligonucleotides specific for the two groups of cDNA clones were used as probes of human liver mRNAs--individual liver samples examined expressed both types of mRNAs but no correlation was observed between the abundance levels of any mRNA and catalytic activity. Further, oligonucleotide probes indicated that mRNAs corresponding to both the MP-4 and MP-8 clones were apparently present in individual liver samples. A monoclonal antibody was isolated that recognized P-450MP-1 but not P-450MP-2 or P-450MP-3; the amount of protein detected by the antibody in different liver samples was not correlated with the mephenytoin 4'-hydroxylase activity. These results indicate that several closely related P-450 genes are all expressed in individual human livers. The MP-4/MP-8 gene products are proposed to be the ones most likely involved in mephenytoin 4'-hydroxylation, and much of the variation in catalytic activity among individuals is not a result of differences in levels of P-450MP-1 or mRNA but may be due to base differences in the structural gene(s).

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Section: Resultsmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase

et al. 1988

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“…liver [147]. However, these P450s show little similarity to the steroidogenic P450c21 and represent products of other genes [25,147]. Immunohistochemical studies using anti-P450c21 antibody revealed a cross reacting protein only in the distal tubules of the bovine kidney, which is the site of the mineralocorticoid action in the kidney [146].…”

Section: P450c21mentioning

confidence: 98%

“…Apart from the adrenal cortex, P450s with steroid 21-hydroxylation activity have been found in other tissues, e.g. liver [147]. However, these P450s show little similarity to the steroidogenic P450c21 and represent products of other genes [25,147].…”

Section: P450c21mentioning

confidence: 99%

“…The dependence of enzyme synthesis on transcriptional induction is most conspicuous in ovarian granulosa cells during follicle growth (see Section 4.5). In vitro studies provide further evidence that trophic hormones can enhance the transcription of genes encoding steroidogenic enzymes: after trophic hormonal stimulation of steroidogenic cells in culture, mRNA levels for steroidogenic enzymes generally increase within a few hours, and reach peak values at 6-12 h (adrenal cortex [38,39,90,99,132,147,234,248], ovary [68,153,224,229,[235][236][237][238][239] testis [40,119,251]).…”

Section: Mechanisms Of Regulation Of Steroidogenic Enzyme Levelsmentioning

confidence: 99%

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Steroidogenic enzymes: Structure, function, and role in regulation of steroid hormone biosynthesis

Hanukoglu

1992

The Journal of Steroid Biochemistry and Molecular Biology

476

278

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In the pathways of steroid hormone biosynthesis there are two major types of enzymes: cytochromes P450 and other steroid oxidoreductases. This review presents an overview of the function and expression of both types of enzymes with emphasis on steroidogenic P450s. The final part of the review on regulation of steroidogenesis includes a description of the normal physiological fluctuations in the steroid output of adrenal cortex and gonads, and provides an analysis of the relative role of enzyme levels in the determination of these fluctuations. The repertoire of enzymes expressed in a steroidogenic cell matches the cell's capacity for the biosynthesis of specific steroids. Thus, steroidogenic capacity is regulated mainly by tissue and cell specific expression of enzymes, and not by selective activation or inhibition of enzymes from a larger repertoire. The quantitative capacity of steroidogenic cells for the biosynthesis of specific steroids is determined by the levels of steroidogenic enzymes. The major physiological variations in enzyme levels, are generally associated with parallel changes in gene expression. The level of expression of each steroidogenic enzyme varies in three characteristics: (a) tissue- and cell-specific expression, determined during tissue and cell differentiation; (b) basal expression, in the absence of trophic hormonal stimulation; and (c) hormonal signal regulated expression. Each of these three types of expression probably represent the functioning of distinct gene regulatory elements. In adult steroidogenic tissues, the levels of most of the cell- and tissue-specific steroidogenic enzymes depend mainly on trophic hormonal stimulation mediated by a complex network of signal transduction systems.

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P ‐450 Cytochromes: Structure and Function

Black

Coon

1987

Advances in Enzymology - And Related Areas of Molecular Biology

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Multiple gene-like sequences related to the rabbit hepatic progesterone 21-hydroxylase cytochrome P-450 1.

Cited by 83 publications

References 44 publications

Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase

Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase

Steroidogenic enzymes: Structure, function, and role in regulation of steroid hormone biosynthesis

P ‐450 Cytochromes: Structure and Function

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