Disease relevance of Cyp11b2

• Physical mapping of overlapping cosmid and phage isolates defined two genes (designated Cyp11b-1 and Cyp11b-2 in the standard nomenclature for cytochrome P450 genes) that are oriented in the same direction and separated by approximately 8 kilobase pairs of DNA [1].
• Accordingly, adrenal glands are enlarged because of hypertrophy of the cortex, resulting in increased expression of key cortical steroid biosynthetic enzymes, such as side-chain cleavage enzyme, steroid 11 beta-hydroxylase, and aldosterone synthase [2].

Psychiatry related information on Cyp11b2

• In a time study experiment we found that P450C11 transformed the labeled-steroid into [14C]corticosterone, [14C]19-OH-deoxycorticosterone and [14C]18-OH-deoxycorticosterone in ratios of 1:1.11:0.07, after 2 h of incubation; no [14C]aldosterone could be detected [3].

High impact information on Cyp11b2

• Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11 beta-hydroxylase [4].
• The mouse gene encoding adrenal steroid 11 beta-hydroxylase (11 beta-OHase) has been cloned and the nucleotide sequence of its 5' end has been determined [4].
• After 2 wk of sodium restriction, plasma aldosterone increased (1.51 +/- 0.27 ng/ml) and potassium remained on average at 4.5 +/- 0.2 mEq/liter, with aldosterone synthase mRNA expressed intensively in Agtr1a+/+, but not detectable in Agtr1a-/- cells [5].
• When animals were fed a normal diet or chronically infused with Ang II, the aldosterone synthase mRNA was detectable only in Agtr1a+/+ but not Agtr1a-/- zona glomerulosa cells [5].
• Additionally, RNase protection assays showed that pituitary POMC cell ablation resulted in the decrease of adrenal p450c11 beta transcripts while p450c11AS (aldosterone synthase) mRNA levels remained constant [6].

Biological context of Cyp11b2

• To study the effects of decreased amounts or absence of aldosterone on development and endocrine function, we have disrupted the mouse gene, Cyp11b2, coding for aldosterone synthase (AS) by replacing its first two exons with sequences coding for enhanced green fluorescent protein [7].
• To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS+/+, AS+/-, and AS-/- mice [8].
• 24 h after transfection, the presence of P450C11 and P450aldo mRNAs was determined by Northern blot analysis [3].
• Both P450C11 and P450aldo cDNA coding sequences were inserted in the plasmid pBluescript SK, transcribed and then translated using a rabbit reticulocyte system in the presence of [35S]methionine [3].
• Gene expression levels of aldosterone synthase and the cardiac aldosterone content were both elevated in the MI hearts, even in AT1A-KO mice [9].

Anatomical context of Cyp11b2

• Aldosterone synthase activity in the Y-1 adrenal cell line [10].
• P450C11 and P450aldo cDNAs were then both inserted into the expression vector pCMV5 containing a viral sequence specific for the attachment of ribosomes to mRNA [3].
• Aldosterone synthase catalyzes the final step in aldosterone biosynthesis and is expressed only in the zona glomerulosa of the normal adrenal [11].

Associations of Cyp11b2 with chemical compounds

• By using polymerase chain reaction, we determined that murine fetal (E14.5-15.5) adrenal glands contain messenger RNAs (mRNAs) encoding all of the steroid hydroxylases required to produce cortisol and corticosterone but little aldosterone synthase mRNA [12].
• Simultaneous sodium restriction and losartan treatment caused increases in plasma potassium (5.5 +/- 0.1 mEq/liter) and aldosterone (1.84 +/- 0.38 ng/ml), with both Agtr1a-/- and Agtr1a+/+ cells intensively expressing aldosterone synthase mRNA [5].

Regulatory relationships of Cyp11b2

• By immunohistochemistry, both number of cells expressing 11beta-hydroxylase and the staining intensity increased in the ACTH-treated glands compared to controls whereas expression of aldosterone synthase was detectable in neither the treated nor control groups [13].

Other interactions of Cyp11b2

• However, in female mice, there was a highly significant positive correlation between blood pressure and AT1A receptor expression, paralleled by significant increases in aldosterone synthase expression with increase in gene copy number [14].

References