Estradiol hydroxylation

Gierthy JF, Lincoln DW, Kampick SJ, et al. 1988. Enhancement of 2- and 16-estradiol hydroxylation in MCF-7 human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem Biophys Res Comm 157 515-520. 

Chronic exposure to cimetidine may be associated with gynecomastia in males and galactorrhea in females, possibly resulting from the drug s affinity for the androgen receptors combined with CYP inhibition of estradiol hydroxylation. Reductions in sperm count and impotence have been described in men chronically receiving the drug. 

Jellinck PH, Forkert PG, Riddick DS, Okey AB, Michnovicz JJ, Bradlow HL. 1993. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem. Pharmacol. 45 1129-36... 

One of the interesting findings with human P450 IBl is that this enz5me is an efficient catalyst of 17p-estradiol hydroxylation and that the pattern is for 4- > 2-hydroxylation This pattern is the opposite of that seen for P450s 1A2 and 3A4 (2- > 4-hydroxylation) and is of significance because 4-hydroxyestradiol is chemically more reactive with oxygen and more likely to oxidize (to O-quinone) and bind DNA. Thus,... 

N.J. Walker, and T.R. Sutter (1996). 17P-Estradiol hydroxylation catalyzed by human cytochrome P450 IBl. Proc. Natl. Acad. Sci. USA 93,9776-9781. 

Nishida CR, Everett S, Ortiz de Montellano PR (2013) Specificity determinants of CYPIBI estradiol hydroxylation. Mol Pharmacol 84 451-458... 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

Isoflavones also have a diphenylpropane structure in which the B ring is located in the C3 position. They have structural analogies to estrogens, such as estradiol, with hydroxyl groups at the C7 and C4 positions (Shier and others 2001). 

Some steroid molecules (estrone, estradiol, and estriol) have phenolic hydroxyl in the ring A (Figure 29.12) and therefore, are able to react as free radical scavengers. In 1987, Japanese authors [264,265] showed that all these compounds inhibited iron adriamycin- or iron ADP-ascorbate-dependent phospholipid and liposomal lipid peroxidation. Later on, most attention was drawn to the study of antioxidative properties of estradiol-17(3 (estrogen E2) it has been proposed that E2 antioxidant activity may contribute to cardioprotection observed after estrogen therapy in postmenopausal women. The necessity for the phenolic hydroxyl has been shown by studying the effects of several estrogens on LDL oxidation. It was found [266]... 

Bulger WH, Kupfer D. 1983a. Effect of xenobiotic estrogens and structurally related compounds on 2-hydroxylation of estradiol and on other monooxygenase activities in rat liver. Biochem Pharmacol 32(6) 1005-1010. 

One of the routes to epimestix>l begins with acylation of estradiol with benzoyl chloride to give the dibenzoate 5. Pyrolysis of the ester leads to formation of the 16,17-olefin. Hydroxylation by means of osmiiim tetroxide affords the cis-diol 7 due to the intermediacy of the cyclic osmate ester (6a)-, attack... 

They have a low incidence of adverse reactions and the reactions that occur are generally mild. Rapid intravenous infusion of H2 antagonists may cause bradycardia. Cimetidine is more inclined to cross the blood-brain barrier and CNS effects such as somnolence and confusion have been described, especially in the elderly and in patients with impaired renal function. Cimetidine in high doses, as the only one of its class, has antiandrogenic effects which could be explained by an increase of prolactin secretion, binding to androgen receptors and inhibition the cytochrome P450 mediated hydroxylation of estradiol. 

Approximately 50% of a dose of mestranol is de-methylated to form ethinyl estradiol. Ethinyl estradiol also can be deethinylated. Subsequently, the metabolism of these two synthetic estrogens proceeds by means of the same pathways as the natural steroid hormones. The principal metabolites of mestranol and ethinyl estradiol are hydroxylated derivatives that are conjugated with either glucuronic acid or sulfate. The synthetic steroid estrogens, in contrast to the natural estrogens, are excreted primarily in the feces. 

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