Metabolism of steroids

PCBs and dioxins are well known for their ability to induce certain iso-enzymes of P450 in the mammalian liver. Some of these iso-enzymes are involved in the metabolism of steroids, and it is possible that changes in rates of metabolism might disturb hormone levels. 

R. Dorfman and F. Ungar, Metabolism of Steroid Hormones, Academic Press, New York, 1965. 

FIGURE 52-6 Biosynthesis/metabolism of steroids in the CNS. The conversion of delta5P to dehydroepiandrosterone (DHA) is postulated but not demonstrated. D5P and DHA inhibit and 3oc,5oc-THP potentiates GABAa receptor function, as summarized in Figure 52-7. Solid arrows indicate demonstrated pathways dotted arrows indicate possible pathways. Metabolic inhibitors of enzymes are indicated by . (Redrawn from [12], with permission.)... 

There are also numerous enzymes anchored in membranes of the microsomal cell fraction that participate in the metabolism of steroid hormones. Thus, those of the p450 family, which carry out molecular oxidation, or the sulfatases and sulfotransferases, more or less specific to several hormones (Pasqualini et al. 1995). The affinity of steroid hormones for proteins of the membrane (Kd between 10 and 100 nM) is frequently greater than that which some of these enzymes present for their substrates (Luzardo et al. 2000). Therefore, it is unlikely that a part of the proteins of the membrane that bind steroids is in reality enzymes metabolizing these hormones. 

A deficiency of liver function reduces metabolism of steroid hormones so that the blood concentration of oestrogens in men is increased. 

Shackleton CH, Honour JW, Dillon MJ, Chantler C, Jones RW (1980c) Hypertension in a four-year-old child gas chromatographic and mass spectrometric evidence for deficient hepatic metabolism of steroids. J Clin Endocrinol Metab 50 786-802... 

Vitamin A (retinol) improves the humoral and cellular tolerance of a person who suffers from an infection. By affecting the differentiation of cells and regulating the metabolism of steroids, vitamin A stimulates the activity of macrophages and T-cytotoxic lymphocytes. It also raises secretion of cytokines and production of antibodies (Hughes 1999, Pfahl and Chytil 1996). 

The inhibition by other organophosphate compounds of the carboxylesterase which hydrolyzes malathion is a further example of xenobiotic interaction resulting from irreversible inhibition because, in this case, the enzyme is phosphorylated by the inhibitor. A second type of inhibition involving organophosphorus insecticides involves those containing the P=S moiety. During CYP activation to the esterase-inhibiting oxon, reactive sulfur is released that inhibits CYP isoforms by an irreversible interaction with the heme iron. As a result, these chemicals are inhibitors of the metabolism of other xenobiotics, such as carbaryl and fipronil, and are potent inhibitors of the metabolism of steroid hormones such as testosterone and estradiol. 

Kaufmann, G., Dautzenberg, H., Henkel, H., et al. 1999. Nitrile hydratase from Rhodococcus erythropolis Metabolization of steroidal compounds with a nitrile group. Steroids, 64 535 0. 

Dorfman and Ungar have given an account of the metabolism of steroid hormones [10], therefore only a few comments v/ill be made here. The comparative relative activities of testosterone metabolities on the seminal vesicle and ventral prostate of immature male rats and capon s comb are summarized in the accompanying table. 

There are several approaches to the study of metabolism. First, isolation of steroid metabolites from various steroid-forming tissues (testes, ovaries, placentae, adrenal glands) makes it possible to evaluate the usefulness of a particular endocrine gland in the production of steroids. Secondly, in vitro experiments are conducted by incubation with tissue preparations followed by isolation of the metabolities of steroids. Thirdly, in vivo experiments are carried out by isolation of steroids from biological fluids, mainly from animal and human blood and urine. This last method includes evaluation of the rates of secretion and metabolism of... 

The biosynthesis of cholesterol, related steroids, and phytosterols is dealt with in this section whereas the further metabolism of these classes and the remaining nonsteroidal triterpenoids are covered in the following two sections. Reviews have appeared on the biosynthesis of sterols and higher terpenoids, the in vivo metabolism of steroids in primates" and in plant tissue culture," and dietary feedback control of cholesterol synthesis." The latter contains a reasoned defence of the hypothesis that HMG-CoA reductase is controlled by alterations to its supporting microsomal membrane. Abstracts of a symposium on all aspects of steroid biosynthesis have appeared." ... 

Several studies are available concerning the metabolism of steroids by insects. It is generally assumed that the Insecta do not synthesize steroids de novo but accumulate them from food this was neatly confirmed for the housefly as [ " CJcholesterol recovered from larvae had the same specific activity as that added to their diet. A... 

JR Gillette. Insights into deuterium isotope effects on the metabolism of steroid hormones and foreign compounds by cytochrome P-450 enzymes. Life Sci 49 1-14, 1991. 

Disease and Drug Protein Binding," and "Toxic Agents Resulting from the Oxidative Metabolism of Steroid Hormones and Drugs." ... 

A bibliography of steroid conjugates as well as a treatise on the metabolism of steroid hormones have been published. The abstracts of papers presented at the Second International Congress of Hormonal Steroids are available. ... 

For many years the metabolism of steroid hormones has been regarded largely as an irreversible detoxicating activity carried out mainly by the... 

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