The selective stimulation, inhibition, and physicochemical alteration of the 7- and 16α-hydroxylases of 3β-hydroxyandrost-5-en-17-one and drug-metabolizing enzymes in hepatic microsomal fractions

Neonatal Effect of Clomiphene and op´-DDT on Hepatic Oxidative Metabolism of Male Rats

“…Hepatic protein and cytochrome P-450 concentrations were also un changed. As expected (3,8), the rates of 16a-7a and 70-hydroxylation and A-demethylation in normal males were significantly (p < 0.05) higher than those of females (table I). Furthermore, the mean rates of these oxidative activities in normal males were slightly increased with age from day 115 to 165.…”

“…The animals were sacrificed at 115 or 165 days of age. Micro somal fractions were prepared and incubations carried out as described previous ly (8). Hepatic 16a-7a-or 70-hydroxylase activities of t4C-dehydroepiandrosterone (DHA) and jV-demethylase activities of aminopyrine were determined by combined radioactivity and gas chromatographic analysis (3) or by colorimetry (8), respectively.…”

“…Specific activities were uncorrected for procedure losses (ap proximately 15 %) and expressed as nmol/min/mg. The microsomal concentra tion of total protein and cytochrome P-450 were measured as before (8).…”

Metabolism of estradiol in liver cell culture. Differential responses of C-2 and C-16 oxidations to drugs and other chemicals that induce selective species of cytochrome P-450.

“…Steroid hormones represent a major class of endogenous compounds metabolized in the liver by cytochrome P-450-dependent monooxygenases in mammals and other species. For example, androgens, such as testosterone and androstenedione, are biotransformed not only by reductive metabolism at the C4-5 double bond, but also by hydroxylation reactions catalyzed by cytochrome P-450 in rat liver (5,6); the substrate specificity and the regulatory mechanisms of these oxidations have been extensively examined (7,8). Differential inducibility of P-450-dependent steroid oxidations has also been demonstrated in trout liver microsomes (9).…”

Neonatal Differentiation of Hepatic DHA 16α- and 7α-Hydroxylases

“…The corresponding control and experimental rates respectively were 2.9 and 1.8 for the 7a-hydroxylase, and 1. and oxygen-dependent activity of microsomal subfractions [4] was in hibited by substrates binding cytochrome P-450 [5] and carbon monoxide2, thus filling the major requirements of mixed-function oxidases [6][7], The testosterone 6(3-, la-, and 16a-hydroxylases share this sex difference and criteria of mixed-function oxidases [8][9][10]. The gonadal control of the steroid 16a-and 7a-hydroxylases is of particular interest because of a number of dissimilarities in the activities of these enzymes.…”