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This version published online on May 8, 2008
Endocrinology, doi:10.1210/en.2008-0183
A more recent version of this article appeared on August 1, 2008
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Submitted on February 7, 2008
Accepted on April 29, 2008

The androgen receptor is selectively involved in organization of sexually dimorphic social behaviors in mice

Cristian Bodo and Emilie F. Rissman*

Department of Biochemistry & Molecular Genetics and Graduate Program in Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908

* To whom correspondence should be addressed. E-mail: Rissman{at}virginia.edu.

It is well established that sexually dimorphic neural regions are organized by steroid hormones during development. In many species, neonatal males are exposed to more testosterone (T) than their female littermates and ultimately it is the estradiol (E2), produced by aromatization of T, that affects sexual differentiation. However, the androgen receptor (AR) also plays an important role in the masculinization of brain and behavior. Here we test the hypothesis that sexually dimorphic social and odor preference behaviors can be differentiated by a non-aromatizable androgen during development by treating female mice on the day of birth (PN0) with dihydrotestosterone (DHT). Control mice received a single vehicle injection on PN0. Adults were gonadectomized, treated with E2, and tested for social behaviors. In contrast with control females, females treated on PN0 with DHT, like male controls, exhibited a preference for female-soiled versus male-soiled bedding, a preference to investigate a female versus a male and reduced c-Fos-immunoreactivity (ir) in several neural areas after exposure to male-soiled bedding. However, females treated with DHT on PN0 had normal female-typical sexual behavior. The number of calbindin-ir cells in the preoptic area is sexually dimorphic, (males>females), but females given DHT on PN0 had intermediate numbers of calbindin-ir neurons, not significantly different from control males or females. Our data demonstrate that organization of social and olfactory preferences in mice can be affected by perinatal DHT and lends support to the role of AR in organization of sexual differentiation of brain and behaviors.


Key words: sex differences • social neuroscience • pheromone • olfaction • sexually dimorphic nucleus • calbindin • sexual orientation







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