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Pattern hair loss: Pathogenesis, clinical features, diagnosis, and management
Published in Jerry Shapiro, Nina Otberg, Hair Loss and Restoration, 2015
Vexiau et al. [77] found abnormal hormone profiles in 67% of women with FPHL and no clinical signs of hyperandrogenism after implementation of β-1-24 corticotropin stimulation test. Especially, 5α-androstane–3α,17β-diol glucuronide levels were found to be elevated in this patient group. 5α-androstane-3α,17β-diol glucuronide is a C19 steroid and reflects the transformation of androgen precursors, mainly of adrenal origin, in women [82]. Increased levels of 5α-androstane–3α,17β-diol glucuronide indicate both splanchnic and extrasplanchnic 5α-reductase hyperactivity [77,83,84].
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
Ethanol-induced elevations in progesterone and corticosterone levels suggest a nonspecific activation of steroid biosynthesis or adrenal release. If pregnane steroid biosynthesis were activated nonspecifically by ethanol, an increase in plasma or brain levels of dehydroepiandrosterone (DHEA) or its sulfated congener, DHEAS, would be predicted. However, systemic ethanol administration (2 g/kg, i.p.) did not alter DHEA or DHEAS levels in several brain regions.62 The lack of effect on ethanol on DHEA and DHEAS levels is consistent with the idea that androstane steroids are differentially regulated than pregnane steroids. Furthermore, these data emphasize the specificity of the effects of ethanol on 3a,5α-THβ and 3a,5α-
The Role of Steroid Sulfatase and Sulfotransferase Enzymes in the Metabolism of C21 and Cl9 Steroids
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
The C19 and C21 steroids that were the most potent inhibitors for the steroid sulfatase in rat and human testes have been identified as metabolic products in studies with testicular preparation from these sources. Payne and Jaffe66 reported the isolation of in incubations of androstenediol-5α-androstane-3β,17β-diol and 5α-androstane-3α,17β-diol in incubations of androstenediol-3-sulfate, with a microsomal preparation from rat testes. They observed that 5α-androstane-3β,17β-diol, which had been shown to be the most potent C19 steroid inhibitor of the sulfatase activity,50 was the most abundant free steroid identified other than testosterone and androstenedione. In studies with isolated seminiferous tubules and minced tissue from human testes, Kawano et al.50 isolated 5-pregnene-3β,20α-diol in incubations with pregnenolone sulfate as the substrate. They demonstrated that steroid sulfatase and 20α reductase, the enzyme that converts pregnenolone to 5-preg-nene-3β,20α-diol, are localized predominantly in seminiferous tubules of the human testes. Payne and co-workers49,67 and Rivarola68 reported that the major concentration of 5α reductase, the enzyme essential for the production of 5α-androstane-3α,17β-diol, is also found predominantly in seminiferous tubules of human testes.
Expression of cytochrome P450 isozyme transcripts and activities in human livers
Published in Xenobiotica, 2021
Jie Liu, Yuan-Fu Lu, J. Christopher Corton, Curtis D. Klaassen
Sex/gender differences in CYP enzymes are a common phenomenon in rodents (Waxman and Holloway 2009). Our Lab recently analysed 78 mouse CYP genes, and sex-dependent expression was observed with 27 CYPs, and 22 CYPs were higher in females including Cyp2a4, Cyp2b9, Cyp2c37, Cyp3a41, and Cyp4a14 (Renaud et al.2011). Human CYP3A4/5 is the most important P450 in human liver because it metabolises the most drugs, and is considered to be female-predominant (Waxman and Holloway 2009). CYP 3A activity can be assessed by midazolam disposition; women exhibited 16% higher weight-corrected midazolam oral clearance than men (Hu and Zhao 2010). In this study, the enzyme activity and mRNA of CYP3A4 as well as CYP2E1 tended to be higher in females. There is also evidence for females having higher activity of CYP2A6 and CYP2B6, but no differences in CPY2C9 and CYP2D6 activity (Anderson 2008). In this study, no major difference in CYP1A2, 2B6, 2C9, 2C19, 2D6, and 4A11 was evident. Sexually dimorphic regulation and induction of P450s could be mediated in part by the constitutive androstane receptor (CAR) (Hernandez et al.2009). Apparently, the dramatic sex-differences in CYP mRNA and enzyme activities seen in experimental animals (Renaud et al.2011) are not observed in humans.
Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans
Published in Xenobiotica, 2018
Jinfang Jiang, Xiaoyan Chen, Dafang Zhong
Anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate) is domestically synthetic, steroid-like estrogen that is used in China as a post-coital contraceptive for more than 30 years (Chih-Ping et al., 1976; Gu et al., 1984). Anordrin is also marketed in combination with mifepristone (Sang et al., 1999). Anordrin is a selective estrogen receptor modulator, with both weak estrogenic and antiestrogenic properties (Mehta et al., 1981,1982; Chatterton et al., 1989). In cynomolgus monkeys, rapid hydrolysis of dipropionate esters is the main metabolic pathway, resulting in forming of unesterified anordriol (Chatterton et al., 1994) (Figure 1). Anordriol shows 36-fold higher affinity than anordrin for cytosol estrogen receptor of rat uterus in vitro, and is the main component responsible for resistance to pregnancy (Gu et al., 1984), thus anordrin can be called as a prodrug for the contraceptive indication. Moreover, α-anordrin shows inhibitory effect on multiple kinds of tumors (Bin et al., 1989; Ma et al., 2000), indicating that anordrin can be developed for variety of potential applications.
Micellar solubilization of poorly water-soluble drugs: effect of surfactant and solubilizate molecular structure
Published in Drug Development and Industrial Pharmacy, 2018
Zahari Vinarov, V. Katev, D. Radeva, S. Tcholakova, N. D. Denkov
Two hydrophobic drugs were used, both products of Sigma-Aldrich (St. Louis, MO): fenofibrate (MW = 360.8 g/mol, purity ≥99%) and danazol (MW = 337.5 g/mol, purity ≥98%). Both drugs have very low water solubility: 1 and 0.8 μg/mL for danazol and fenofibrate, respectively [9,30], and belong to Class II of the Biopharmaceutical classification system [31]. The model non-polar substance 5α-androstane was obtained from Sigma-Aldrich (MW = 260.5 g/mol, purity ≥99%). The molecular structures of the three studied substances are presented in Figure 1.