Elsevier

Hormones and Behavior

Volume 64, Issue 2, July 2013, Pages 203-210
Hormones and Behavior

Review
Sexual differentiation of the adolescent rodent brain: Hormonal influences and developmental mechanisms

https://doi.org/10.1016/j.yhbeh.2013.05.010Get rights and content

Highlights

  • The brain is further sexually differentiated during puberty and adolescence.

  • Ovarian hormones play an active role in neural feminization during puberty.

  • These effects have been found in hypothalamic, limbic, and cortical regions.

  • Hormonal and region specific loss and addition of neurons and glia occur.

Abstract

This article is part of a Special Issue “Puberty and Adolescence”.

Sexual differentiation is the process by which the nervous system becomes structurally and functionally dissimilar in females and males. In mammals, this process has been thought to occur during prenatal and early postnatal development, when a transient increase in testosterone secretion masculinizes and defeminizes the developing male nervous system. Decades of research have led to the views that structural sexual dimorphisms created during perinatal development are passively maintained throughout life, and that ovarian hormones do not play an active role in feminization of the nervous system. Furthermore, perinatal testosterone was thought to determine sex differences in neuron number by regulating cell death and cell survival, and not by regulating cell proliferation. As investigations of neural development during adolescence became more prominent in the late 20th century and revealed the extent of brain remodeling during this time, each of these tenets has been challenged and modified. Here we review evidence from the animal literature that 1) the brain is further sexually differentiated during puberty and adolescence; 2) ovarian hormones play an active role in the feminization of the brain during puberty; and 3) hormonally modulated, sex-specific addition of new neurons and glial cells, as well as loss of neurons, contribute to sexual differentiation of hypothalamic, limbic, and cortical regions during adolescence. This architectural remodeling during the adolescent phase of sexual differentiation of the brain may underlie the known sex differences in vulnerability to addiction and psychiatric disorders that emerge during this developmental period.

Section snippets

Sexual differentiation of hypothalamic regions during adolescence: the anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN)

The AVPV and SDN of adult rats are sexually dimorphic, with the AVPV being larger in females than in males (female-biased) and the SDN being larger in males (male- biased). The AVPV is essential for the generation of the sexually differentiated pattern of gonadotropin releasing hormone (GnRH) secretion, as it coordinates the preovulatory GnRH and luteinizing hormone (LH) surge (Petersen and Barraclough, 1989, Wiegand and Terasawa, 1982), a neuroendocrine event displayed by female rats only

Sexual differentiation of the posterodorsal medial amygdala (MePD) during adolescence

The rodent MePD evaluates chemosensory stimuli from conspecifics and integrates this information with the internal hormonal milieu, thereby coordinating the external and internal signals that regulate social behaviors. MePD volume is larger in adult male rats than in female rats, with this sex difference being more pronounced in the right hemisphere than in the left (Cooke and Woolley, 2005, Cooke et al., 2007, Morris et al., 2008). This adult sexual dimorphism is the product of two successive

Sexual differentiation of the cerebral cortex and its connectivity during adolescence

Structural sex differences in the cerebral cortex are not as visually prominent or as large in magnitude as those in the hypothalamus where the earliest investigations of sexual differentiation of the nervous system were focused. Nevertheless, there are sex differences in the cortex and in its connections. Notably, many of the sex differences emerge during puberty as the result of exposure to ovarian hormones in females.

Sexual differentiation of the locus coeruleus (LC) during adolescence

The LC is a group of midbrain neurons that are the primary source of norepinephrine in the central nervous system and therefore this cell group has a pivotal role in the regulation of mood, basal arousal, and anxiety. The adult female rat LC is larger in volume and has more neurons than the LC of the adult male rat (Guillamon et al., 1988). This sex difference arises as the result of two postnatal periods during which growth of the female LC outpaces that of the male: the first period occurs

Conclusions

It is now clear that the creation of structural sex differences during perinatal development is just the first phase of morphological sexual differentiation of the nervous system. A second phase of sexual differentiation occurs during puberty, when gonadal hormones are once again elevated, this time in both the developing male and female. This second, pubertal, phase of sexual differentiation may be a mechanism for maintaining or establishing for the first time structural and functional sexual

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