China
Africa
Explore chapters and articles related to this topic
Environmental Androgens and Antiandrogens: An Expanding Chemical Universe
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
L. Earl Gray, Vickie Wilson, Tammy Stoker, Christy Lambright, Johnathan Furr, Nigel Noriega, Phillip Hartig, Mary Cardon, Mitch Rosen, Gerald Ankley, Andrew Hotchkiss, Edward F. Orlando, Louis J. Guillette, William R. Kelce
Procymidone is a dicarboximide fungicide similar in structure to vinclozolin. Hosokawa et al.8 demonstrated in a competitive binding assay that procymidone effectively inhibited the binding of [3H]-DHT to the androgen receptor in both rats and mice. Ostby et al.26 demonstrated that procymidone inhibited DHT-induced transcriptional activation at 0.2 µM in CV-1 cells cotransfected with the human AR and a MMTV-luciferase reporter gene, while at 10 µM, DHT-induced transcriptional activity was completely inhibited. In addition, 1 µM procymidone blocked DHT-induced AR-DNA binding in a CHO cell promoter interference assay. Although it is likely that metabolites of procymidone, rather than procymidone itself, are the true AR antagonists, the metabolites studied to date have not displayed affinity for AR.8
Retardation of Preputial Wound Healing in Rats with Hypospadias Induced by Flutamide
Published in Journal of Investigative Surgery, 2020
Yue Zhou, Jinpu Peng, Xining Cao, Chao Yan, Fangyuan Huang, Lianju Shen, Chunlan Long, Xing Liu, Guanghui Wei
Hypospadias in these rats can be induced by prenatal treatment with various compounds [1, 5]. Hypospadias in the rat has been induced by phthalates, which are known to inhibit androgen production by the testes, including: Di (n-butyl) phthalate, di-isobutyl phthalate, di-isooctyl phthalate, di-(2-ethylhexyl) phthalate, di-n-hexyl phthalate, and a phthalate mixture [5]. Hypospadias has also been reported in rats following prenatal treatment with the estrogen, diethylstilbestrol, an effect that in part may be due to reduced androgen production by the testes [6]. Other agents that induce hypospadias in rats include the 5α-reductase inhibitor, finasteride, androgen receptor antagonists, such as flutamide, vinclozolin, procymidone (alone or in combination), and p,p′-DDE [7]. Flutamide is an androgen receptor antagonist. Multiple studies have found that hypospadias can be induced by flutamide, which is a widely accepted drug to establish a hypospadiac model [8, 9]. The wound healing process involves in a variety of cytokines, such as transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMactin), and signal transducers and activators of the transcription 3 (STAT3). These cytokines are involved in many processes in early stage of wound repair, including cell proliferation, tissue reconstruction, and angiogenesis [10]. In this study, we compared the prepuce healing process (prepuce is considered an important urethral replacement in operative repair) in Sprague-Dawley (SD) rats with and without hypospadias, induced by flutamide.
In vitro phase I metabolism of vinclozolin by human liver microsomes
Published in Xenobiotica, 2019
Marycarmen Cruz-Hurtado, Ma de Lourdes López-González, Victor Mondragón, Adolfo Sierra-Santoyo
Regarding Vin toxicity in humans, there is only one report in which M3 was used as a biomarker of Vin exposure, but no association between anti-androgenic or reproductive effects and urinary M3 levels was reported in an occupational setting of Vin exposure (Zober et al., 1995). The absence of an association in this study may be due to M3 is not a specific metabolite of V since it is also produced from other dicarboximides, such as procymidone, iprodione and chlozolinate (Lindh et al., 2007; Wittke et al., 2001). In a pilot study conducted in a rural province of China (Zhejiang), in which 20 non-persistent pesticides were analyzed by gas chromatography-mass spectrometry, Vin and acetochlor cord blood levels were significantly associated with reduced birth weight (Wickerham et al., 2012). Despite the limited information in humans and assuming a similar in vivo dose-response relationship and a temporal association supported by its mechanism of action, Vin effects observed on the reproductive tract of male animals are highly plausible in humans (Kavlock & Cummings, 2005). This proposal is supported by the fact that despite Vin instability in physiological conditions, it has been identified in blood of umbilical cords and adult people, and placenta samples (Molina-Molina et al., 2006; Wickerham et al., 2012).