Disease relevance of Cyp21a1

• Hyperprolactinemia did not influence microsomal 3B-HSD or mitochondrial 11-OHase activities but was associated with a dose dependent decrease in microsomal 21-OHase activity when compared to controls (p less than 0.001) [1].

High impact information on Cyp21a1

• The levels of 3betaHSD, P450C21, and P450C11 mRNA did not differ from control values in that zone [2].
• Western blotting analysis showed that the adrenal ZG protein levels of StAR and P450scc were increased (150%), 3betaHSD was not changed, and P450C21 was decreased by 70% [2].
• The changes in steady-state levels of mRNA for cholesterol side-chain cleavage cytochrome P-450 (P-450scc) and steroid 21-hydroxylase cytochrome P-450 (P-450c21) caused by hypophysectomy and ACTH treatment were determined in rat adrenals [3].
• The steroid 21-hydroxylase activity of liver microsomes decreased with treatment by sodium phenobarbital or beta-naphthoflavone and was inhibited by anti-cytochrome b5 immunoglobulin, although that of adrenocortical microsomes was not [4].
• Organ specificities of cytochrome P-450s21 (steroid 21-hydroxylase) were investigated [4].

Chemical compound and disease context of Cyp21a1

• Adrenal cytosol progesterone levels increased with increasing rPRL dose consistent with a 21-OHase block during hyperprolactinemia [1].

Anatomical context of Cyp21a1

• Steroid 21-hydroxylase expression in cultured rat astrocytes [5].
• Biphasic regulation by N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) of steroid 21-hydroxylase activity in rat hepatocytes [6].
• These findings indicate that the steroid 21-hydroxylase in rat liver is regulated by mechanisms different from those in the adrenal glands [6].
• In the adrenal cortex, steroid 21-hydroxylase activity is increased by corticotropin (ACTH); the effect of ACTH is mediated by cyclic AMP (cAMP), and presumably involves a cAMP-dependent protein kinase (PKA) [6].

Associations of Cyp21a1 with chemical compounds

• However, different from human and mouse, a copy of the C4, Cyp21, and Stk19 genes is found that maps to the class II region in the rat [7].
• Dog PBD-2 metabolizes progesterone primarily to the 21-OH metabolite, while metabolism by rat PB-B leads to the formation of the 16 alpha-OH product [8].
• Rat adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase (3-HSD), 21-hydroxylase (21-OH) and 11-hydroxylase (11-OH) activities decreased with increasing RU486 doses, with 21-OH and 11-OH being most severely affected [9].
• High local activity with no side effects, equivalent to that of 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon), is obtained when either the 17- or 21-OH of halopredone are benzoylated [10].

Physical interactions of Cyp21a1

• Subsequent extractions with chloroform and methanol showed inhibition of substrate binding and conversion with hydrophobic compounds exhibiting a greater inhibitory effect on deoxycorticosterone binding to CYP11B1 (30%) and on progesterone binding to CYP21 (50%) [11].

Other interactions of Cyp21a1

• A 35% decrease in adrenal microsomal cytochrome P-450 21 and NADPH-cytochrome P-450 reductase levels was brought about by the treatment with MAD [12].
• Water extracts showed inhibition of substrate binding to cytochrome P450 21-hydroxylase (CYP21) by 38% and cytochrome P450 11beta-hydroxylase (CYP11B1) by 60% [11].
• These data suggest that prolactin has a direct effect on rat adrenal 21-OHase in vivo [1].

Analytical, diagnostic and therapeutic context of Cyp21a1

• Both P-450scc and P-450c21 mRNAs were decreased by hypophysectomy and increased by ACTH treatment [3].

References