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Hydroxylated C18 and C19 Steroids; Their Significance and Factors Related to Their Biosynthesis
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
The binding affinity of rat uterine cytosol and chromatin preparations for 2-hydroxyestradiol is reportedly 25% that of estradiol.40 This binding does not appear to be related to an estrogenic response, since the catechol estrogen exhibits < 1% of the uterotropic activity of estradiol.41 Moreover, 2-hydroxyestrone, with only 0.1% of the uterotropic activity of estrone,42 has been shown40 to possess 20% of the binding affinity of the latter steroid. In contrast to this, certain other steroids showing little or no uterotropic activity, such as 2-methoxy phenolic steroids and estetrol [estra-1,3,5(10)-triene-3, 15α, 16α, 17β-tetrol], are bound scarcely at all to the rat uterine receptors in vitro. It has been suggested40 that these data imply an antiestrogenic role for the 2-hydroxysteroids. It is of interest to note that, in a study reported in 1955,43 2-hydroxyestradiol was demonstrated to possess 1% of the uterotropic activity of estradiol in vivo in the oophorectomized rat and in the mouse. Nevertheless, the same catechol estrogen considerably stimulated formate incorporation into uterine protein in vitro as compared with the effect of estradiol.
The effect of carbamazepine, which increases oestrogen destruction, on the endometriotic implants; an experimental rat model
Published in Journal of Obstetrics and Gynaecology, 2022
Mehmet Bulbul, Mehmet Can Nacar, Bilge Aydin Turk, Talip Karacor, Muhittin Onderci, Ali Parlar, Pınar Kirici, Cihat Ucar
Oestrogen acts on the body through itself and its metabolites. Although it has different metabolites, it is generally metabolised to 2-hydroxyestradiol by the CYP3A4 enzyme in the liver and peripheral tissues (Liehr and Ricci, 1996; Shou et al. 1997). Many studies have shown that 2-hydroxyestradiol can prevent cancer development (Fotsis et al. 1994; Klauber et al. 1997). In contrast, 4-hydroxyestradiol, another oestrogen metabolite, contributes to carcinogenesis through free oxygen radicals (Lemon et al. 1992; Nutter et al. 1994; Liehr and Ricci, 1996). CMZ is known to decrease the efficiency of contraceptives by increasing CYP3A4 activity—hence, oestrogen degradation (Gaffield et al. 2011; Guillemette and Yount, 2012; Reimers et al. 2015; Herzog et al. 2016; Reddy 2017, 2010; Hole et al. 2018; Lutz et al. 2018; Ke et al. 2019). With this effect of CMZ, oestradiol levels in target tissues decrease and 2-hydroxyestradiol levels increase. This change in oestradiol/2-hydroxyestradiol balance may protect the target tissues against the adverse effect of oestrogen. In our study, endometrial hyperplasia developed in three rats in the EV group, but no endometrial hyperplasia formation was found in the EV + CMZ group, supporting this information.
SNP’s in xenobiotic metabolism and male infertility
Published in Xenobiotica, 2020
Neslihan Hekim, Mohamed Ali Gure, Asli Metin Mahmutoglu, Sezgin Gunes, Ramazan Asci, Ralf Henkel
We found an elevated frequency of CYP1A2 AA genotype in infertile group compared to normozoospermic/fertile controls (p = 0.056, p for trend = 0.0229). Within our knowledge, the present study is the first study investigating the association between CYP1A2 C > A polymorphism and male infertility (Zanger and Schwab, 2013). Besides the role in the metabolism of xenobiotics, CYP1A2 along with other CYP enzymes, has specific endogenous functions in elimination of estrogens (Croom, 2012). 2-hydroxyestradiol, a major metabolite of estradiol, is mainly catalyzed by CYP1A2 in the liver. Alterations in estrogen level might be involved in testicular cancer development and infertile men are at the elevated risk of developing testicular cancer (Hanson et al., 2018; Vistisen et al., 2004). Therefore, the association of CYP1A2 gene polymorphism with testicular cancer suggests a potential role in male infertility.
Effect of Dietary Flaxseed Intake on Circulating Sex Hormone Levels among Postmenopausal Women: A Randomized Controlled Intervention Trial
Published in Nutrition and Cancer, 2019
Vicky C. Chang, Michelle Cotterchio, Beatrice A. Boucher, David J. A. Jenkins, Lucia Mirea, Susan E. McCann, Lilian U. Thompson
Although exact mechanisms are unclear, it has been postulated that flaxseed/lignans may alter the profile of estrogen metabolites by modifying the expression or activity of cytochrome P450 enzymes responsible for estrogen hydroxylation to favor 2- over 16-hydroxylation (24,31,57). For example, flaxseed supplementation in hens upregulated CYP1A1 expression, resulting in increased and decreased production of 2- and 16α-hydroxyestrone, respectively (57). However, while the 2:16α-hydroxyestrone ratio has been inversely associated with breast cancer risk and suggested as a potential target for dietary interventions (24), recent research indicated that overall and relative abundances of 2-, 4-, and 16-hydroxylation pathway metabolites may be more relevant with respect to breast cancer risk and prevention (21–23,58,59). Our study additionally assessed 2-methoxyestrone and estriol (2- and 16-hydroxylated, respectively) and found no significant changes related to flaxseed intake. These results are in line with those of Sturgeon et al., who examined three other metabolites (2-hydroxyestradiol, 2-methoxyestradiol, and 4-hydroxyestradiol) in urine and reported no changes except for a statistically significant decline in 2-methoxyestradiol (33).