Inhibition of rat testicular 17α-hydroxylase and 17,20-lyase activities by anti-androgens (flutamide, hydroxyflutamide, ru23908, cyproterone acetate) in vitro

Ayub, Mohammad; Levell, M. J.

doi:10.1016/0022-4731(87)90122-1

Cited by 65 publications

(41 citation statements)

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“…The parameters included common endpoints such as male reproductive organ weight, anogenital indicate an inhibition of enzymes involved in the conversion of progesterone to testosterone and might be due, at least partly, to inhibition of CYP17 (Laier et al, 2006), an effect that has been confirmed in vitro in H295R cells and in testicular microsomes (Blystone et al, 2007;Ayub and levell, 1987;Ohlsson et al, 2010). the increased progesterone levels in the dams are suggested to cause virilization of the female offspring (Taxvig et al, 2007), which would explain the increased AGD in females Tab.…”

Section: Conazolementioning

confidence: 99%

Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

Dreisig

2013

ALTEX

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Section: Conazolementioning

confidence: 99%

Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

Dreisig

2013

ALTEX

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Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…These data also suggest reciprocal interactions between ARs and ERs in the brain, a theme emphasized in the remainder of this review. The AR antagonist flutamide is also an imperfect test of AR contributions since its administration, while blocking ARs, also alters T production from the testes, making it difficult to attribute changes in morphology and behavior solely to AR blockade (Clos et al, 1988;Ayub and Levell, 1987).Testicular feminization mutant (Tfm) rodents provide a unique model for examining the role of the ARs in the brain and behavior, because this mutation in the AR gene renders the protein nonfunctional. As a result of this mutation (the rodent analog of CAIS in humans), genetically male Tfm rodents appear phenotypically female: they possess nipples typical of female rodents, lack normal male genitalia, and are infertile.…”

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confidence: 99%

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

Zuloaga

Puts

Jordan

et al. 2008

Hormones and Behavior

213

156

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Many studies demonstrate that exposure to testicular steroids such as testosterone early in life masculinizes the developing brain, leading to permanent changes in behavior. Traditionally, masculinization of the rodent brain is believed to depend on estrogen receptors (ERs) and not androgen receptors (ARs). According to the aromatization hypothesis, circulating testosterone from the testes is converted locally in the brain by aromatase to estrogens, which then activate ERs to masculinize the brain. However, an emerging body of evidence indicates that the aromatization hypothesis cannot fully account for sex differences in brain morphology and behavior, and that androgens acting on ARs also play a role. The testicular feminization mutation (Tfm) in rodents, which produces a nonfunctional AR protein, provides an excellent model to probe the role of ARs in the development of brain and behavior. Tfm rodent models indicate that ARs are normally involved in the masculinization of many sexually dimorphic brain regions and a variety of behaviors, including sexual behaviors, stress response and cognitive processing. We review the role of ARs in the development of the brain and behavior, with an emphasis on what has been learned from Tfm rodents as well as from related mutations in humans causing complete androgen insensitivity. Keywordscomplete androgen insensitivity syndrome -CAIS; vasopressin; anxiety; spatial memory; bed nucleus; medial amygdala; SDN-POA; sexual behavior; aggression; VMH Exposure to testicular steroids such as testosterone (T) early in life masculinizes the developing brain, leading to permanent changes in behavior in a wide variety of animal models (Morris et al., 2004). According to the aromatization hypothesis, T is converted by aromatase into 17-β estradiol (E2), which then acts on estrogen receptors (ERs) to masculinize the brain (Naftolin et al., 1975). Traditionally, aromatization is believed to be the mechanism by which the rodent brain becomes masculinized and defeminized. Some sexually dimorphic regions within the hypothalamus adhere well to this hypothesis, including the sexually dimorphic nucleus of the preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV). T spares neuronsCorresponding author: Damian Zuloaga, Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824, Phone: Fax: (517) 432-2744, Email: E-mail: zuloagad@msu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript from death in the SDN-POA...

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“…The drug acts mainly at the peripheral level blocking competitively the cytoplasmic and nuclear binding of androgens to the receptor (7,9). Additional effects in reducing androgen synthesis (10) and increasing androgen metabolism to inactive molecules (11) have also been shown.…”

Section: Introductionmentioning

confidence: 99%

Retrospective observational study on the effects and tolerability of flutamide in a large population of patients with various kinds of hirsutism over a 15-year period

Paradisi¹,

Venturoli²

2010

European Journal of Endocrinology

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Objective: The aim of the study was to evaluate the long-term effects and tolerability of flutamide (Flu) in hirsute women. To the best of our knowledge, this study represents the largest report, concerning the population studied and the duration of treatment, to evaluate Flu use in hirsutism treatment. Design, patients and methods: Over a 15-year period spanning from January 1991 to January 2006, a total of 414 premenopausal women with hirsutism of different aetiopathogeneses received yearly reducing doses (250, 125 and 62.5 mg/day) of Flu alone or in combination with oral contraceptives for a period varying from at least 3 to 8 years and more. Clinical and endocrine evaluations were assessed half-yearly and yearly respectively in the first 3 years of the study, and yearly in the following years. Liver function evaluations were assessed quarterly. Results: Both the groups of patients under Flu therapy showed a marked decrease in hirsutism scores after 12 months compared with basal values. The maximum drug effect was observed after 2 years, and it was maintained during the following years of treatment. Androgens were strongly suppressed during treatment. During the first year of treatment, 6.0% of patients abandoned the study due to hepatic disorders related to the drug. During the following years with the lowest treatment regimen, none of the patients abandoned the study due to hepatic discomfort. Conclusions: Flu is a satisfactory therapeutic regimen for any form of hirsutism in the long run. Moreover, the use of very low doses of Flu is associated with minimal side-effects and high compliance.

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Inhibition of rat testicular 17α-hydroxylase and 17,20-lyase activities by anti-androgens (flutamide, hydroxyflutamide, ru23908, cyproterone acetate) in vitro

Cited by 65 publications

References 15 publications

Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

Retrospective observational study on the effects and tolerability of flutamide in a large population of patients with various kinds of hirsutism over a 15-year period

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