The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development

Abstract

Adolescence is a developmental period characterized by dramatic changes in cognition, risk-taking and social behavior. Although gonadal steroid hormones are well-known mediators of these behaviors in adulthood, the role gonadal steroid hormones play in shaping the adolescent brain and behavioral development has only come to light in recent years. Here we discuss the sex-specific impact of gonadal steroid hormones on the developing adolescent brain. Indeed, the effects of gonadal steroid hormones during adolescence on brain structure and behavioral outcomes differs markedly between the sexes. Research findings suggest that adolescence, like the perinatal period, is a sensitive period for the sex-specific effects of gonadal steroid hormones on brain and behavioral development. Furthermore, evidence from studies on male sexual behavior suggests that adolescence is part of a protracted postnatal sensitive period that begins perinatally and ends following adolescence. As such, the perinatal and peripubertal periods of brain and behavioral organization likely do not represent two discrete sensitive periods, but instead are the consequence of normative developmental timing of gonadal hormone secretions in males and females.

Keywords: Activational-organizational hypothesis; Adolescence; Agonistic behavior; Anxiety-like behavior; Cortex; Estrogen; Ingestive behavior; Sensitive periods; Sexual behavior; Synaptic pruning; Testosterone.

Figure 1

The Two-stage model of postnatal brain and behavioral development. The lines depict the time course for endogenous secretions of testosterone (dotted line) in males and estradiol in females (solid line) across postnatal development. The boxes highlight the times in which endogenous gonadal steroid hormones typically organize the developing brain. The shading indicates, based on current empirical evidence, sensitivity to the organizing actions of gonadal steroid hormones decreases across postnatal development. Note that while substantial evidence suggests that both male and female behaviors are organized by adolescent exposure to gonadal steroid hormones, the evidence thus far for decreasing sensitivity to the organizing actions of hormones across postnatal development is primarily in males in a limited number of species. Therefore, further testing of this empirical model may reveal a different pattern of sensitivity to gonadal steroid hormones in sexes of additional species.

Figure 2

Effects of periadolescent testosterone exposure on adult reproductive behaviors. Testosterone treatments were designed to simulate early, on-time, and late pubertal development, and all behavior testing occurred in adulthood. Only pre- and mid-adolescent testosterone treatments facilitated mounting behavior in response to testosterone in adulthood. Adult intromissive behavior was only increased by pre-adolescent testosterone treatments. These data suggest that early testosterone treatments enhance behavioral responsiveness to testosterone in adulthood. Asterisk indicates a significant difference (p<0.05) between groups. Adapted from Schulz et al., (2009), Endocrinology 150 (9) 3690–3698.

Figure 3

Mean number of mounts, intromissions and ejaculations displayed by sexually inexperienced males that were deprived of testicular hormones during adolescence (GDX during adolescence) and males exposed to testicular hormones during adolescence (intact during adolescence; GDX in adulthood) and tested for reproductive behavior 7 weeks later. All males were administered T for one week prior to behavior tests. All values are expressed as means ± SEM. Adapted from Schulz et al., (2004) Hormones and Behavior 45 (4) 242–249.

Figure 4

(A) Mean number of flank marks exhibited by adult males deprived of testicular hormones during adolescence (GDX during adolescence) and males exposed to testicular hormones during adolescence (intact during adolescence; GDX in adulthood). Adult testosterone treatment significantly increased flank marking behavior during a resident/intruder test in males who were gonad-intact during adolescence (GDX in adulthood) but not males where were GDX prior to adolescence. (B&C) Photomicrographs of V1a receptor binding in the lateral septum (LS) of two testosterone-treated adult males that were either deprived of gonadal hormones during adolescence (B) or exposed to gonadal hormones during adolescence (C). Males deprived of gonadal hormones during adolescence (B) displayed significantly greater V1a receptor binding than males exposed to gonadal hormones during adolescence (C). Adapted from Schulz et al., (2006), Hormones and Behavior 50 (3) 477–483.

Figure 5

Mean number of flank marks across 6 trials is dependent on an interaction between pubertal testosterone, status and trial number. Status only affected the number of flank marks in males that were exposed to testicular hormones during adolescence (intact; GDX and T-replaced in adulthood), with dominant males flank marking significantly more than no-status and subordinate intact males (+ = p < 0.05). There were no differences between no-status, subordinate or dominant males that were deprived of testicular hormones during adolescence (GDX during adolescence) and T-replaced in adulthood prior to behavioral testing. Adapted from Delorme and Sisk (2013), Physiology & Behavior (112–113) 1–7.

Figure 6

Pubertal ovarian hormones defeminize lordosis behavior. Females were exposed to (intact during adolescence; OVX in adulthood) or deprived of ovarian hormones during adolescence (OVX during adolescence). All females were estradiol and progesterone primed in adulthood prior to behavioral testing with a stud male. Females exposed to ovarian hormones during adolescence (intact) displayed significantly longer lordosis latencies than females deprived of adolescent ovarian hormones (OVX) when both groups were estradiol and progesterone primed and paired with a male in adulthood. Asterisk indicates P < 0.05. Adapted from Schulz and Sisk (2006), Molecular and Cellular Endocrinology (254–255) 120–126.

Figure 7

New cells are added during puberty to the AVPV, SDN and medial amygdala in male and female rats. Left photomicrographs, thionin-stained sections; right photomicrographs, BrdU labeled cells in nearby sections from the same rat; insets, BrdU-labeled cells framed in small boxes at x10 higher magnification. Rats received a daily injection of 300 mg per kg body weight of BrdU on three consecutive days at either 20–22, 30–32 or 40–42 d of age (n ¼ 6–8 per age and sex). BrdU is incorporated into DNA during the S phase of the cell cycle and can be later visualized to identify cells replicating at the time of BrdU administration. Brain tissue was collected 20 d after the first BrdU injection, on 40, 50 or 60 d of age, respectively. Quantitative analyses of BrdU-labeled cells revealed that during puberty, significantly more cells were added to AVPV (A) in females than in males, whereas significantly more cells were added to SDN (B) and medial amygdala (Me; C) in males than in females. Data are means ± s.e.m. Scale bars, 250 mm in lower-magnification images. Adapted from Ahmed et al., (2008), Nature Neuroscience 11 (9) 995–997.

Figure 8

The number of neurons in the ventral portion of the male and female mPFC at P35 and in adulthood at P90. There was a loss of neurons in females between these ages, resulting in a sex difference in adulthood. n = 9–11 per group, * indicates p ≤ 0.02. Redrawn with permission from Markham et al., (2007), Neuroscience (144) 961–968.