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. 1999 Jun 22;96(13):7538-40.
doi: 10.1073/pnas.96.13.7538.

A brain sexual dimorphism controlled by adult circulating androgens

B M Cooke  1 , G Tabibnia, S M Breedlove
Affiliations

A brain sexual dimorphism controlled by adult circulating androgens

B M Cooke et al. Proc Natl Acad Sci U S A. .

Abstract

Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a possible confounding variable is the concentration of circulating hormones seen in these groups in adulthood. Evaluation of this possibility hinges on the extent to which circulating hormones can alter the size of mammalian brain regions as revealed by Nissl stains. We now report a sexual dimorphism in the volume of a brain nucleus in rats that can be completely accounted for by adult sex differences in circulating androgen. The posterodorsal nucleus of the medial amygdala (MePD) has a greater volume in male rats than in females, but adult castration of males causes the volume to shrink to female values within four weeks, whereas androgen treatment of adult females for that period enlarges the MePD to levels equivalent to normal males. This report demonstrates that adult hormone manipulations can completely reverse a sexual dimorphism in brain regional volume in a mammalian species. The sex difference and androgen responsiveness of MePD volume is reflected in the soma size of neurons there.

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Figures

Figure 1
Figure 1
Photomicrograph of a Nissl-stained section indicating the boundaries of the MePD.
Figure 2
Figure 2
Mean (± SEM) unilateral volume of MePD in rats 4 wk after sham surgery (Left) or castration followed by T treatment or no hormone (blank). Adult T treatment of castrated rats eliminated the sex difference in MePD volume. Either sex, when treated with T, displayed MePD volumes that did not differ significantly from those of control males, indicating that adult circulating androgen concentration was the sole factor determining sexual dimorphism of MePD volume. Two-way ANOVA of castrates revealed a significant main effect of treatment (F(1, 20) = 7.1, P < 0.0002), but none for sex, (F(1, 20) = 1.6, P = 0.21) or interaction.
Figure 3
Figure 3
Among control animals, MePD somata were significantly larger in males (two-tail t test, P = 0.05). Gonadectomy and implantation of a blank Silastic capsule reduced the size of these neurons in males. Implantation of a capsule packed with T increased soma size in females, again eliminating the difference. Two-way ANOVA among the gonadectomized groups revealed a significant main effect of T (F(1, 18) = 21.5; P < 0.0003) but none for sex (P > 0.05) or any significant interaction.
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