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| THE ROLE OF ANDROGENS IN BEHAVIORAL SEX DIFFERENCES S. Marc Breedlove, Ph.D., Psychology Department, University of California, Berkeley, California There have been reports of sex differences in a remarkably wide variety of behaviors in both humans and non-human animals. These sex differences are almost always more subtle in humans than in other animals, and even in non-human animals there tends to be considerable overlap between the male and female sub-populations. Nevertheless, nearly all of the sex differences in animal behaviors can be accounted for by gonadal steroid hormones, especially androgens such as testosterone. A good deal has been learned recently about how androgens affect the nervous system and how those effects result in changes in behavior. Most of these studies have not examined pain perception, but rather have focused on reproductive behaviors. However, a discussion of the mechanisms by which androgens affect reproductive behaviors suggests possible ways in which these hormones might affect other behaviors such as pain perception. Steroid hormones play a crucial role in sexual differentiation of the mammalian body and the major principles of that process are clearly similar in humans and non-human species. In sum, sex chromosomes direct the development of the indifferent gonads into either ovaries or testes. If testes develop, they secrete hormones that direct the body to form a masculine phenotype. In the absence of testes, these hormones are not produced and the body responds by forming a feminine phenotype. In non-human animals the same gonadal steroids that masculinize the body also masculinize the brain and therefore behavior. In some cases the steroids must act early in development in order to permanently alter nervous system structure by affecting the production, migration, survival or phenotype of neurons in specific regions at particular stages of development. Such effects of steroids are often characterized as "organizational". In other cases the steroids can act upon the nervous system throughout life, even in adulthood, in order to alter the nervous system and therefore behavior. In those cases the steroids are said to exert an "activational" effect, and usually these effects consist of changes in the number and/or quality of synapses. We have been studying several different animal models where steroids can affect neuronal structure and therefore behavior. In the rat spinal cord, androgens act early in life to spare motoneurons from ontogenetic cell death (apoptosis), and also act upon the motoneurons in adulthood to increase the number and size of synaptic inputs to these motoneurons. In the rat brain, we have confirmed a previously reported sexual dimorphism in the volume of the medial amygdala, and have also found a sex difference in the size of neurons in the posterodorsal portion of the medial amygdala (MePD). It appears that these sexual dimorphisms can be entirely accounted for by circulating levels of androgen in adulthood. Finally, in a seasonally breeding rodent, the Siberian hamster, we have found that exposure to light, specifically the length of light seen each day, can drastically affect circulating androgen levels and therefore neural structure. These steroid effects on rodents suggest mechanisms by which hormones might engender human sex differences in pain perception.
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