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.The 1959 landmark paper by Phoenix, Goy, Gerall, and Young first posited what became the organizational-activational hypothesis of hormone-driven sex differences in brain and behavior (Phoenix et al., 1959). In this hypothetical framework, a transient rise in testosterone during prenatal or early postnatal development masculinizes and defeminizes neural circuits in males, while the absence of testosterone in females results in development of a feminine neural phenotype. Upon gonadal maturation during puberty, testicular and ovarian hormones act on previously sexually differentiated circuits to facilitate expression of sex-typical behaviors in particular social contexts. Research in the 1960-70s identified a maximally sensitive period for hormone-dependent sexual differentiation that occurs during late prenatal and early neonatal development (reviewed in Baum, 1979;Wallen and Baum, 2002). Thus, the original conception was that steroid hormones organize brain structure during an early developmental sensitive period, and activate behavior during puberty and into adulthood.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

The adolescent brain: Changes and challenges of development

“…The activation effect occurs in puberty as hormones affect the dormant neural circuits. These events are also involved in organizing the neurocircuitry of adult social and reproductive behavior (13). The changes of cortical grey matter in density, volume and thickness during childhood and adolescence, happen in a region-specific and predominately nonlinear manner.…”

Interactions Between Reproductive and Immune Systems During Ontogeny: Roles of GnRH, Sex Steroids, and Immunomediators

“…As noted above, the brain retains its plasticity at later stages, and its responsiveness to sex steroids in males reaches a second peak during adolescence. Such a peak during the late postnatal period is also characteristic of females, but its exact timing has not yet been determined for them (Shulz et al, 2009). …”

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