Cytochrome p450 steroid hormone biosynthesis

Apparent combined P450C17 and P450C21 deficiency (see 613571) is a rare variant of congenital adrenal hyperplasia, first reported by Peterson et al. (1985). Affected girls are born with ambiguous genitalia, indicating intrauterine androgen excess. After birth, however, virilization does not progress and amounts of circulating androgens are low or normal. Affected boys are sometimes born undermasculinized. Boys and girls can also present with bone malformations. Findings of biochemical investigations of urinary steroid excretion in affected patients have shown accumulation of steroid metabolites, indicating impaired C17 and C21 hydroxylation, suggesting concurrent partial deficiencies of the 2 steroidogenic enzymes, P450C17 and P450C21. However, sequencing of the genes encoding these enzymes showed no mutations, which accorded with the idea of a defect in a cofactor that interacts with both enzymes.

In a multi-center 6-week study, Fux et al (2005) examined the impact of CYP2D6 polymorphism on the tolerability of metoprolol in a primary care setting.  The adverse effects studied comprised effects related to the central nervous system, cardiovascular effects, and sexual dysfunction.  The dosage of metoprolol was determined on an individual basis and could be adjusted on clinical grounds.  The indication for treatment was hypertension in about 90 % of cases.  CYP2D6 genotyping covered alleles *3 to *10 and *41 and the duplications.  Possible ADRs of metoprolol were systematically assessed over the study period using standardized rating scales and questionnaires.  The final study population comprised 121 evaluable patients: 5 ultrarapid metabolizers (UMs) ( %), 91 extensive metabolizers (EMs) (75 %), 21 intermediate metabolizers (IMs) (17 %), and 4 poor metabolizers (PMs) ( %).  Plasma metoprolol concentrations normalized for the daily dose and metoprolol/alpha-hydroxymetoprolol ratios at steady state were markedly influenced by CYP2D6 genotype and displayed a gene-dose effect.  The median of the dose-normalized metoprolol concentration was ng/ml, ng/ml, ng/ml, and ng/ml among UMs, EMs, IMs, and PMs, respectively (p < ).  There was no significant association between CYP2D6 genotype-derived phenotype (EMs and UMs combined versus PMs and IMs combined) and ADRs during treatment with metoprolol.  There was a tendency toward a more frequent occurrence of cold extremities in the PM plus IM group as compared with the EM plus UM group ( % versus %, p = ; relative risk, [95 % confidence interval [CI]:  to ]).  These investigators concluded that CYP2D6 genotype-derived phenotype was not significantly associated with a propensity for ADRs to develop during treatment with metoprolol.  However, the results concerning tolerability of metoprolol in PMs were inconclusive because of the small number of PMs enrolled.

Cytochrome p450 steroid hormone biosynthesis

cytochrome p450 steroid hormone biosynthesis

Media:

cytochrome p450 steroid hormone biosynthesiscytochrome p450 steroid hormone biosynthesiscytochrome p450 steroid hormone biosynthesiscytochrome p450 steroid hormone biosynthesiscytochrome p450 steroid hormone biosynthesis

http://buy-steroids.org