The Orthodox View of Brain Sexual Differentiation

Abstract

The standard view of sexual differentiation of the brain, derived primarily from work with mammals, is that the same steroidal signal which permanently masculinizes the body early in life, androgen, also permanently masculinizes the nervous system. This oversimplified view overlooks the rich diversity of mechanisms produced by natural selection. We review the mechanisms underlying sexual differentiation of what may be the simplest mammalian model, the spinal nucleus of the bulbocavernosus (SNB), a system that is intimately associated with sexual differentiation of the periphery. Indeed, in many instances, early androgen can permanently masculinize the SNB system but, surprisingly, these early influences may depend to some extent on social mediating factors. Furthermore, in adulthood, androgen continues to affect the SNB system in diverse ways, acting on several different loci, indicating a life-long plasticity in even this simple system. Finally, there is evidence that adult androgens interact with social experience in order to affect the SNB system. Thus the SNB system displays a far richer array of interactions than the standard view of sexual differentiation would predict. Examination of other systems and other species, as depicted in the following reports, reveals a far more complicated, and far more interesting perspective on how the brains and behaviors of males and females diverge.

Testosterone in utero and at birth dictates how stressful experience will affect learning in adulthood

“…Moreover, the absence of testosterone shortly after birth organizes the ability to acquire trace memories in adulthood and dictates its modulation by stressful experience in females. These effects are generally consistent with those of sexual behaviors, which become masculinized by exposure to testosterone in utero and feminized by its absence shortly after birth (3,9,33,34). Our data suggest that sexually dimorphic effects of emotional experience on cognitive behaviors in adulthood are similarly organized by a relatively brief exposure to testosterone during development.…”

Hormones and borderline personality features

“…Hormonal factors in prenatal life promote the sexual differentiation of the mammalian brain and the expression of sex-linked reproductive and social behavior, such that higher levels of androgens in prenatal life are associated with the expression of more male-typical behavior across a variety of species (Breedlove et al, 1999). In humans, increasing evidence indicates that prenatal hormones also contribute to the behavioral variability between (and within) the sexes and the subsequent responsiveness of some behaviors to fluctuations in postpubertal sex steroid levels (Collaer & Hines, 1995).…”

Sexual dimorphism in digit‐length ratios of laboratory mice

“…This ratio is indeed sexually dimorphic in humans: men have a smaller 2D:4D ratio on average than do women. The sex difference in the 2D:4D ratio is evident, and stable, from 2 years of age though adulthood (Manning et al, 1998).Since the 2D:4D ratio sex difference appears to be unaffected by changing sex hormone levels at puberty, and since most other mammalian sex differences are androgen-dependent (Breedlove et al, 1998), prenatal androgen levels may play a role in digit length development. Supporting this supposition is the finding that individuals with congenital adrenal hyperplasia (CAH) display masculinized finger length patterns (Brown et al, 2001).…”