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Enzymes, aromatase

The enzyme aromatase catalyses the conversion of testosterone to estrogen. A number of in vitro studies have shown that phytoestrogens can inhibit aromatase (Adlercreutz et al, 1993 Kao et al, 1998 Pelissero et al, 1996). However, the high concentrations required to cause this effect in vitro are unlikely to be achieved in vivo following dietary exposure. [Pg.68]

Drugs that can be used to control tumour cell proliferation inhibit a variety of enzymes, including thymidylate synthase and topoisomerase (Chapter 20). The enzyme aromatase converts a ring in a steroid to an aromatic ring. It converts, for example, adrenal steroid hormones into female sex hormones, which bind to oestrogenic receptors in the ovary or breast and increase the risk of ovarian or breast cancer. Aromatase inhibitors are used to treat patients with breast or ovarian cancers that are sensitive to oestrogen. Unfortunately, none of the inhibitors is specific for enzymes in tumour cells and they can therefore have severe side-effects (Chapter 21). [Pg.60]

Figure 19.8 A brief summary of the pathways for formation and secretion of oestradiol and progesterone within the cells of the follicle. Cholesterol is taken up by thecal cells in a complex with low density lipoprotein. In the thecal cells, cholesterol is converted to testosterone which is released to be taken up by granulosa cells where it is converted into oestradiol. For synthesis of progesterone in the granulosa cells, cholesterol is synthesised de novo within the cells from acetyl-CoA. In the follicle the enzyme aromatase, which produces the aromab c ring in the female sex hormones, is restricted to the granulosa cells. The reacrions that are stimulated by LH and FSH increase synthesis and, therefore, secretion of testosterone and increased synthesis of oestrogens and progesterone. Figure 19.8 A brief summary of the pathways for formation and secretion of oestradiol and progesterone within the cells of the follicle. Cholesterol is taken up by thecal cells in a complex with low density lipoprotein. In the thecal cells, cholesterol is converted to testosterone which is released to be taken up by granulosa cells where it is converted into oestradiol. For synthesis of progesterone in the granulosa cells, cholesterol is synthesised de novo within the cells from acetyl-CoA. In the follicle the enzyme aromatase, which produces the aromab c ring in the female sex hormones, is restricted to the granulosa cells. The reacrions that are stimulated by LH and FSH increase synthesis and, therefore, secretion of testosterone and increased synthesis of oestrogens and progesterone.
One approach to interfere with ER signalling is to reduce the circulating level of its ligand estradiol by inhibiting the enzyme aromatase. Aromatisation is the last step in the synthesis of estradiol. This reaction is catalysed by the P450 aromatase mono-oxygenase complex that is present in the smooth endoplasmic... [Pg.34]

Recanatini, M., Bisi, A., Cavalli, A., et al. (2001) A new class of nonsteroidal aro-matase inhibitors design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C 17,20-lyase. ./. Med. Chem. 44, 672-680. [Pg.517]

The third way testosterone affects fat synthesis is not positive. When testosterone levels are elevated, more is converted into estrogens by way of the conversion enzyme aromatase. This is called aromatization, an important word to understand before reading the rest of this book Estrogen in turn increases female pattern fat deposits and suppresses HPTA function. Atleast estrogen can increase GH production. [Pg.10]

Hormone synthesis can be altered by changes in the size and population of hormone producing cells, modification of the activity of hormone synthesizing enzymes, lack of precursors, or interference with enzyme cofactors such as divalent cations. Eor example, the fungicide fenarimol inhibits the enzyme aromatase, which converts testosterone to estrogen. Exposures to acrylamide monomer induce changes in the volume of cellular components in the thyroid... [Pg.983]

In a similar fashion, it is evident that the estrogen screen described above, could be modified to include enzymes required for the synthesis or degradation of estradiol. An alternative therapeutic objective for estradiol inhibition might be to prevent its synthesis. Thus, a yeast strain already built to be sensitive to estradiol could be supplied instead with the precursor to estradiol, 19-nortestosterone, and the enzyme, aromatase, required for its conversion to estradiol. An inhibitor of the enzyme would, therefore, lead to the inability to synthesize estradiol and the loss of production of 3-galactosidase. [Pg.115]

Testosterone and other androgens can be converted into the female hormone estrogen by the enzyme aromatase. [Pg.117]

Sasano H, Okamoto M, Mason JI, et al. Immunohistochemical studies of steroidogenic enzymes (aromatase, 17 alpha-hydroxylase and cholesterol side chain cleavage cytochrome P450) in sex cord stromal tumors of the ovary. Hum Pathol. 1989 20 452-457. [Pg.330]

Estrogens are a class of female sex hormones that include estrone and estradiol. As shown in Figure 19.24, estrogens are derived from the androgens (male sex hormones) by action of the enzyme aromatase. [Pg.1257]

Ahmed, S., S. Adat, A. Murrells, C.R Owen, and Y. Amanuel (2002). Design, synthesis, and evaluation of 4-(4 )-aminobenzyl)-2-oxazolidinones as novel inhibitors of the cytochrome P-450 enzyme aromatase. Bioorg. Chem. 30, 315-331. [Pg.316]

Testosterone is an intermediate in the biosynthesis of oestradiol. The conversion, which involves three successive hydroxylations and the loss of a methyl group, is catalysed by the enzyme aromatase. Aromatase has three catalytic activities 19-hydroxylase, 19-hydroxysteroid dehydrogenase and... [Pg.174]


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See also in sourсe #XX -- [ Pg.30 ]




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