Cytochrome P-450 and steroid biosynthesis in the human placenta

Cytochromes P‐450 and bs in human liver microsomes

“…7 Although the presence of cytochromes P-450 and b 5 has been amply documented in experimental ani-mals, the evidence for their presence in man has been scant. Recently, the hemoprotein P-450 was detected in human term placenta, 14 but no information has been presented on the presence of this hemoprotein in human liver. Results presented in this paper show that cytochromes P-450 and b 5 are present in human liver and have spectral characteristics similar to those already reported in animals.…”

Regiospecificity of Placental Metabolism by Cytochromes P450 and Glutathione S-Transferase

“…P450 19A1 (aromatase) is responsible for the conversion of androgens to estrogens [2,16,17], In our study, aroma tase activity was observed in all fractions tested with the highest activity (1.92 ± 0.2 pmol/min/pg protein) occur ring in WT and the lowest activity (1.63 ± 0.37 pmol/ min/pg protein) found in PM and this difference was sta tistically significant (p < 0.05). This variation of enzy matic activity may have an anatomical explanation in that the syncytiotrophoblasts, which line the placental vil li and are thought to be responsible for estrogen synthesis [22] , have a reduced density in the margins of the placen ta.…”

“…Studies of placental tissue homogenates and subfrac tions have shown that several of the known drug-metabo lizing enzyme systems are present in the placenta, al though at considerably lower activities than in the liver [1][2][3][4], For example, P450 1A1 activity, which can convert the polycyclic aromatic hydrocarbons in cigarette smoke to reactive metabolites, has been observed in the placenta and, interestingly, is induced by cigarette smoke [5,6]. The placenta, via cytochrome P450 19A1 (aromatase), is also a major source of estrogens during pregnancy [7,8].…”

Biological Aspects of Cytochrome P450 and Associated Hydroxylation Reactions

“…The production of pregnenolone from cholesterol by the placenta [123,127] also appears to be located in the mitochondrial fraction [100]. In this tissue, however, the 19-hydroxylase (and aromatase) activities are more equally distributed between the rough-and smooth-surfaced microsomes [142], It is seen that the mitochondrial steroid hydroxylating activities of the endocrine tissues consist of the hydroxylations relating to the conversion of cholesterol to pregnenolone and thence to progesterone, and llß-and 18-hydroxylations [52,106,112].…”

“…Cytochrome P450 has been identified as participating in steroid hydrox ylation reactions in the adrenal cortex [90], corpus luteum of the ovary [87,89,143], testis [36,96] and placenta [100,125], The protein has been identified in both the mitochondria [87,90,96,100] and microsomes [89,90,96,100,158] of these organs. These species of cytochrome P450 are concerned with hydroxylation steps in the biosynthesis of steroid hormones, the pattern of elaboration of which is influenced considerably by a variety of factors such as the metabolic state, age and sex of the individual [9,122,126,142].…”