Flutamide and Cyproterone Acetate Exert Agonist Effects: Induction of Androgen Receptor-dependent Neuroprotection.
From: University of Southern California, Davis School of Gerontology, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
Endocrinology
- Publish Date: Jun 2007
- ISSN: 0013-7227
- Volume: 148
- Issue: 6
- Pages: 2936-43
- Medium: Print
- Language: English
- Citation (JAMA): Nguyen Thuy-Vi V, Yao Mingzhong, Pike Christian J, et al. Flutamide and Cyproterone Acetate Exert Agonist Effects: Induction of Androgen Receptor-dependent Neuroprotection.. Endocrinology Jun 2007;148:2936-43
Abstract
Androgens can exert profound effects on the organization, development, and function of the nervous system through activation of androgen receptors (ARs). Nonsteroidal and steroidal antiandrogens antagonize AR-mediated, classic genomic actions of androgens. However, emerging studies in nonneuronal cells indicate that antiandrogens can act as partial agonists for the AR. Here we investigated the effects of the antiandrogens flutamide and cyproterone acetate on neuroprotection induced by dihydrotestosterone (DHT). We observed that, although flutamide and cyproterone acetate blocked androgen-induced gene expression, they failed to inhibit DHT protection against apoptotic insults in cultured hippocampal neurons. Interestingly, flutamide and cyproterone acetate alone, like DHT, significantly reduced apoptosis. Furthermore, the protective actions of flutamide and cyproterone acetate were observed specifically in AR-expressing cell lines, suggesting a role for AR in the agonist effects of antiandrogens. Our results indicate that, in contrast to the classic antiandrogen properties of flutamide and cyproterone acetate, these AR modulators display agonist activities at the level of neuroprotection. These findings provide new insight into the agonist vs. antagonist properties of antiandrogens, information that will be crucial to understanding the neural implications of clinically used AR-modulating drugs.
Mesh Headings (Keywords): Androgen Antagonists, Animals, Animals, Newborn, Cyproterone Acetate, Flutamide, Gene Expression Regulation, Molecular Mimicry, Neurons, Neuroprotective Agents, PC12 Cells, Rats, Rats, Sprague-Dawley, Receptors, Androgen
Check for Full Text / PubMed Unique Identifier (PMID): 17347309
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