Back to the future: The organizational-activational hypothesis adapted to puberty and adolescence

Abstract

Phoenix, Goy, Gerall, and Young first proposed in 1959 the organizational-activational hypothesis of hormone-driven sex differences in brain and behavior. The original hypothesis posited that exposure to steroid hormones early in development masculinizes and defeminizes neural circuits, programming behavioral responses to hormones in adulthood. This hypothesis has inspired a multitude of experiments demonstrating that the perinatal period is a time of maximal sensitivity to gonadal steroid hormones. However, recent work from our laboratory and others demonstrates that steroid-dependent organization of behavior also occurs during adolescence, prompting a reassessment of the developmental time-frame within which organizational effects are possible. In addition, we present evidence that adolescence is part of a single protracted postnatal sensitive period for steroid-dependent organization of male mating behavior that begins perinatally and ends in late adolescence. These findings are consistent with the original formulation of the organizational/activational hypothesis, but extend our notions of what constitutes "early" development considerably. Finally, we present evidence that female behaviors also undergo steroid-dependent organization during adolescence, and that social experience modulates steroid-dependent adolescent brain and behavioral development. The implications for human adolescent development are also discussed, especially with respect to how animal models can help to elucidate the factors underlying the association between pubertal timing and adult psychopathology in humans.

Fig 1

Two stage model for steroid-dependent organization of behavior. Testosterone secretions during the perinatal and adolescent periods organize adult mating behavior. The dashed line approximates testosterone secretions across development, and the shading denotes the approximate timing of perinatal and adolescent development in the Syrian hamster. The question mark highlights that less is known about T-dependent behavioral organization in the time between the perinatal and adolescent periods.

Fig 2

Effects of early, on-time, and late adolescent treatments (blank or testosterone-filled capsules) on adult mating behavior. All animals were testosterone treated in adulthood prior to behavior testing. Early and on-time adolescent testosterone treatments, but not late-adolescent treatments facilitated mounting behavior relative to blank-treated controls (data expressed as mean +/− SEM). In contrast, only early adolescent testosterone-treatment facilitated intromissive behavior relative to blank-treated controls, suggesting that early adolescent treatments most effectively organize mating behavior (data expressed as percent). Asterisk indicates p < 0.05.

Fig 3

Illustration depicting the overall findings of our study investigating the effects of early, on-time, and late adolescent testosterone treatments on adult mating behavior. Given that early adolescent testosterone treatment was initiated immediately following the period of sexual differentiation (postnatal day 10), our data suggest that adolescence is part of a protracted sensitive period for the organizing actions of testosterone (area under the solid gray curve). In addition, because early adolescent treatments most effectively organized adult mating behavior, we propose that sensitivity to the organizing actions of testosterone decreases across postnatal development. The dashed line approximates testosterone secretions across development, whereas the solid line depicts decreasing sensitivity to the organizing actions of testosterone across development. Shading approximates the timing of perinatal, prepubertal, adolescent periods in the Syrian hamster.

Fig 4

Theoretical illustration depicting how early or late pubertal onset intersects the developing brain at different time points. Because sensitivity to the organizing actions of T decreases with time, differences in the timing of pubertal onset may result in differences in brain development and adult behavior. The dashed lines depict early or late testosterone secretions across development, whereas the solid line depicts decreasing sensitivity to the organizing actions of testosterone across development. Shading approximates the timing of perinatal, prepubertal, adolescent periods in the Syrian hamster.

Fig 5

Adolescent social experience restores adult ejaculatory behavior in male Syrian hamsters lacking pubertal testosterone. In the absence of social experience, males gonodectomized (GDX) before puberty displayed significantly fewer ejaculations than positive control males GDX after puberty. However, adolescent social experience with a female partially restored ejaculation number in males GDX before puberty to the levels of the positive control group. Exposure to the mesh box alone did not restore ejaculations to the level of positive controls. Asterisk indicates p<0.05.