58: Sexual Differentiation of the Nervous System

Introduction

• Genes and Hormones Determine Physical Differences Between Males and Females

  • Chromosomal Sex Directs the Gonadal Differentiation of the Embryo

  • Gonads Synthesize Hormones That Promote Sexual Differentiation

  • Steroid Hormones Act by Binding to Specific Receptors

• Sexual Differentiation of the Nervous System Generates Sexually Dimorphic Behaviors

  • A Sexually Dimorphic Neural Circuit Controls Erectile Function

  • A Sexually Dimorphic Neural Circuit Controls Song Production in Birds

  • A Sexually Dimorphic Neural Circuit in the Hypothalamus Controls Mating Behavior

• Environmental Cues Control Some Sexually Dimorphic Behaviors

  • Pheromones Control Partner Choice in Mice

  • Early Experience Modifies Later Maternal Behavior

• Sexual Dimorphism in the Human Brain May Correlate with Gender Identity and Sexual Orientation

• An Overall View

Few words are more loaded with meaning than the word "sex." Sexual activity is a biological imperative and a major human preoccupation. The physical differences between men and women that underlie partner recognition and reproduction are obvious to all of us, and their developmental origins are well understood. In contrast, our understanding of behavioral differences between the sexes is primitive. In many cases their very existence remains controversial, and the origins of those that have been clearly demonstrated remain unclear.

In this chapter we first briefly summarize the embryological basis of sexual differentiation. We then discuss at greater length the behavioral differences between the two sexes, focusing on those differences or dimorphisms for which some neurobiological basis has been found. These dimorphisms include physiological responses (erection, lactation), drives (maternal behavior), and even more complex behaviors (gender identity). In analyzing these dimorphisms we will discuss three issues.

First, what are the genetic origins of sexual differences? Human males and females have a complement of 23 chromosomal pairs, and only one differs between the sexes. Females have a pair of X chromosomes (and are therefore "XX"), whereas males have one copy of the X chromosome paired with a Y chromosome (XY). The other 22 chromosome pairs, called autosomes, are shared between males and females. We will see that some genetic determinants arise from the presence of a Y chromosome, while others arise from sex-specific patterns of autosomal gene expression that exert their impact during development.

Second, how are differences in genes and gene expression translated into differences between the brains of men and women? We will see that key intermediates are the sex hormones, a set of steroids that includes testosterone and estrogens. These hormones act during embryogenesis as well as postnatally, first organizing the physical development of both genitalia and brain regions, and later activating particular physiological and behavioral responses. Hormonal regulation is especially complex because the nervous system, which is profoundly influenced by sex steroids, also controls their synthesis. This feedback loop may help to explain how the external environment, including social and cultural factors, can ultimately shape sexual dimorphism at a neural level.

Third, what are the crucial neural differences that underlie sexually dimorphic behaviors? ...