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Gene Review:

Cyp11b1 - cytochrome P450, family 11, subfamily b,...

Rattus norvegicus

Synonyms: CYPXIB1, Cp11ba, Cyp11b-1, Cytochrome P450 11B1, mitochondrial, Cytochrome P450(11 beta)-DS, ...

Garrett, M.R. et al., Cicila, G.T. et al., Lehoux, J.G. et al., Matsukawa, N. et al., Veltman, J.C. et al., et al.

Garrett, Rapp,

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Disease relevance of Cyp11b1

The pathogenesis of this form of experimental hypertension is thought to result from inhibition of steroid 11 beta-hydroxylase activity [1].

High impact information on Cyp11b1

One of these (CYP11B1) encodes P450c11 beta, which is the steroid 11 beta-hydroxylase found solely in the adrenal zona fasciculata/reticularis, and is responsible for the conversion of 11-deoxycorticosterone to corticosterone [2].
When the two cDNAs were expressed in COS-7 cells and steroid conversion rates of the transformed cells were determined, a ratio of 18-hydroxylation to 11 beta-hydroxylation of 11-deoxycorticosterone by P450(11 beta)-DS-expressed cells was 0.58, whereas that by P450(11 beta)-DR-expressed cells was 0.23 [3].
This effect is believed to be mediated through the adrenal gland and in particular by action on the steroid 11 beta-hydroxylase enzyme system [4].
The levels of 3betaHSD, P450C21, and P450C11 mRNA did not differ from control values in that zone [5].
Few changes were observed in the adrenal protein contents of cholesterol side-chain cleavage cytochrome P450 (P450scc), cytochrome P450 11beta-hydroxylase (P450C11), cytochrome P450 21-hydroxylase (P450C21), and 3beta-hydroxysteroid dehydrogenase (3betaHSD) [5].

Biological context of Cyp11b1

In the present work we have constructed a final congenic substrain that retains a blood pressure effect and that has an introgressed congenic segment which includes Cyp11b1 and is < 177 kb in size [6].
In the present work, interval mapping identified a putative blood pressure quantitative trait locus (QTL) near Cyp11b1 in an F1(SxR)xS population (LOD = 2.0) [7].
Defining the blood pressure QTL on chromosome 7 in Dahl rats by a 177-kb congenic segment containing Cyp11b1 [6].

Anatomical context of Cyp11b1

In the mitochondria, 1 day after Cu2+ treatment, when the concentration of the metal ion was increased by 2- to 3-fold over the control value, a significant increase in cytochrome P-450-dependent steroid 11 beta-hydroxylase activity was observed [8].

Associations of Cyp11b1 with chemical compounds

In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11 beta-hydroxylase [9].
The present findings suggest that decreased expression of steroid 11 beta-hydroxylase could contribute to the increased secretion of 11-deoxycorticosterone during the early stages of adrenal regeneration [10].
The increase in mitochondrial cytochrome P-450 content was reflected in elevated steroid 11 beta-hydroxylase and cholesterol side-chain cleavage activities [11].
The data establish that the preferential decrease in adrenal steroid 11 beta-hydroxylase activity associated with androgen treatment results from a decrease in cytochrome P-450 11 beta [12].
The inhibition of steroid 11 beta-hydroxylase by metyrapone, racemic metyrapol, (-)-metyrapol or (+)-metyrapol was analyzed in rat adrenal homogenates [13].

Other interactions of Cyp11b1

This suggests that the increased survival of S.R-Cyp11b rats was largely due to their decreased blood pressure and thus strongly corroborates the existence of a blood pressure QTL on Chr 7 near or at Cyp11b1 [7].

Analytical, diagnostic and therapeutic context of Cyp11b1

We believe that we have reached the limit of resolution for congenic analysis of a QTL in a rodent animal model, and we conclude that Cyp11b1 causes the observed QTL on rat Chr 7 in Dahl rats [6].

References

The inhibition of rat adrenal cytochrome P-45011 beta gene expression by androgens. Gallant, S., Alfano, J., Charpin, M., Brownie, A.C. Endocr. Res. (1992) [Pubmed]
P450c11B3 mRNA, transcribed from a third P450c11 gene, is expressed in a tissue-specific, developmentally, and hormonally regulated fashion in the rodent adrenal and encodes a protein with both 11-hydroxylase and 18-hydroxylase activities. Mellon, S.H., Bair, S.R., Monis, H. J. Biol. Chem. (1995) [Pubmed]
Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11 beta), but the salt-sensitive hypertensive rat does not. Matsukawa, N., Nonaka, Y., Higaki, J., Nagano, M., Mikami, H., Ogihara, T., Okamoto, M. J. Biol. Chem. (1993) [Pubmed]
Expression of adrenal cytochromes P-450 in testosterone-induced hypertension. Gallant, S., Alfano, J., Charpin, M., Brownie, A.C. Hypertension (1991) [Pubmed]
The acute and chronic effects of adrenocorticotropin on the levels of messenger ribonucleic acid and protein of steroidogenic enzymes in rat adrenal in vivo. Lehoux, J.G., Fleury, A., Ducharme, L. Endocrinology (1998) [Pubmed]
Defining the blood pressure QTL on chromosome 7 in Dahl rats by a 177-kb congenic segment containing Cyp11b1. Garrett, M.R., Rapp, J.P. Mamm. Genome (2003) [Pubmed]
Blood pressure and survival of a chromosome 7 congenic strain bred from Dahl rats. Cicila, G.T., Dukhanina, O.I., Kurtz, T.W., Walder, R., Garrett, M.R., Dene, H., Rapp, J.P. Mamm. Genome (1997) [Pubmed]
Regulatory effect of copper on rat adrenal cytochrome P-450 and steroid metabolism. Veltman, J.C., Maines, M.D. Biochem. Pharmacol. (1986) [Pubmed]
Selective thromboxane synthetase inhibitors. 4. 2-(1H-imidazol-1-ylmethyl) carboxylic acids of benzo[b]furan, benzo[b]thiophene, indole, and naphthalene. Cross, P.E., Dickinson, R.P., Parry, M.J., Randall, M.J. J. Med. Chem. (1986) [Pubmed]
Cytochromes P-45011 beta, P-450scc and adrenodoxin gene expression during adrenocortical regeneration in the rat. Chou, F.P., Gallant, S., Brownie, A.C. J. Endocrinol. (1989) [Pubmed]
Alterations of heme, cytochrome P-450, and steroid metabolism by mercury in rat adrenal. Veltman, J.C., Maines, M.D. Arch. Biochem. Biophys. (1986) [Pubmed]
Levels of adrenodoxin, NADPH-cytochrome P-450 reductase and cytochromes P-45011 beta, P-45021, P-450scc, in adrenal zona fasciculata-reticularis tissue from androgen-treated rats. Brownie, A.C., Bhasker, C.R., Waterman, M.R. Mol. Cell. Endocrinol. (1988) [Pubmed]
Stereoselective reductive metabolism of metyrapone and inhibitory activity of metyrapone metabolites, metyrapol enantiomers, on steroid 11 beta-hydroxylase in the rat. Nagamine, S., Horisaka, E., Fukuyama, Y., Maetani, K., Matsuzawa, R., Iwakawa, S., Asada, S. Biol. Pharm. Bull. (1997) [Pubmed]

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