Neonatal RU-486 (mifepristone) exposure increases androgen receptor immunoreactivity and sexual behavior in male rats
Abstract
Progesterone and progestin receptors (PRs) are known to play a role in the development of brain physiology and behavior in many different species. The distribution and regulation of PRs within the developing brain suggest that they likely contribute to the organization of the brain and behavior in a sex-specific manner. We examined the role of PR signaling during development on the organization of adult sexual behavior and androgen receptor (AR) expression in the brain. We administered the PR antagonist, RU-486, subcutaneously to male and female rats on postnatal days 1-7 (0=day of birth) and examined adult sexual behavior and AR-immunoreactivity (AR-ir) in the adult brain. A typical sex difference in lordosis quotient (LQ) was observed and neonatal RU-486 treatment did not alter this behavior. In contrast, neonatal RU-486 treatment increased adult male sexual behavior and AR-ir in several brain areas in males. These data indicate that a transient disruption in PR signaling during development can have lasting consequences on the male brain and may increase male sexual behavior in part by increasing AR expression, and therefore androgen sensitivity, in adulthood.
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Blocking PRs using RU-486 during development increases male sex behavior and AR expression in several regions of the adult male brain.
“blocking PRs using RU-486 during development increases male sex behavior and the expression of ARs in several regions of the adult male brain [10]”
From Sex-specific effects of neonatal progestin receptor antagonism on juvenile social play behavior in rats (2021) · cites this paper as [10]
The treatment regimen is similar to what has been previously used for RU-486.
“This treatment regimen is similar to what has been previously used for RU-486 [10]”
From Sex-specific effects of neonatal progestin receptor antagonism on juvenile social play behavior in rats (2021) · cites this paper as [10]
Cites
Brain masculinization requires androgen receptor function
Sato, T., Matsumoto, T., Kawano, H., Watanabe, T., Uematsu, Y., Sekine, K., Fukuda, T., Aihara, K.-I., Krust, A., Yamada, T., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305303101 · Cited by 303 · see citing works
Distribution of progesterone receptor immunoreactivity in the fetal and neonatal rat forebrain
Quadros, P. S., Pfau, J. L., & Wagner, C. K. (2007) · Journal of Comparative Neurology · doi:10.1002/cne.21427 · Cited by 112 · see citing works
Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression
Forbes-Lorman, R. M., Rautio, J. J., Kurian, J. R., Auger, A. P., & Auger, C. J. (2012) · Epigenetics · doi:10.4161/epi.7.3.19265 · Cited by 43 · see citing works
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Forbes-Lorman, R. M. (2021) · Behavioral and Brain Functions · doi:10.1186/s12993-021-00183-z · Cited by 1 · see citing works
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- Authors
- Forbes-Lorman, R., Auger, A. P., & Auger, C. J.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 1543
- Pages
- 143-150
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2042237322
- Cited by
- 12
- References
- 3
- Citations by year
- 2023: 1 · 2021: 2 · 2019: 1 · 2017: 3 · 2016: 4 · 2015: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (NSF) (IOS-1122074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- RU486, mifepristone, progesterone receptor, androgen receptor, neonatal drug exposure, sexual differentiation of the brain, male sexual behavior, sex differences, androgen sensitivity, postnatal development
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Brain, Female, Hormone Antagonists, Male, Receptors, Androgen, Sexual Behavior, Animal, Sex Characteristics, Mifepristone, Rats, Sprague-Dawley, Rats
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