The Organizational-Activational Hypothesis

Critical Periods in Development

Permanent vs Temporary Hormonal Effects

The Prenatal Testosterone Surge in Male Development

Congenital Adrenal Hyperplasia (box)

Androgen Insensitivity Syndrome (box)

Pubertal Changes in Brain Structure

Menstrual Cycle Effects on Brain Function

Pregnancy Effects on Brain Function

Contraceptive Effects on Brain Function

Menopause Effects on Brain Function

The organizational-activational concept is a foundational framework in behavioral neuroendocrinology that explains how hormones influence the development of sex-typical behaviors and characteristics through two distinct phases.

Organizational Effects

The organizational phase occurs during critical developmental periods, primarily during prenatal development and early postnatal life. During this time, hormones (particularly androgens like testosterone) permanently “organize” or structure the brain and other tissues in sex-typical ways. These effects:

• Are irreversible once the critical period closes
• Create lasting structural differences in brain regions, neural circuits, and peripheral tissues
• Establish the biological foundation for later sex-typical behaviors and responses
• Occur through mechanisms like cell proliferation, migration, differentiation, and programmed cell death

For example, prenatal testosterone exposure masculinizes certain brain regions and creates the neural substrate that will later support male-typical behaviors when activated by hormones.

Activational Effects

The activational phase occurs throughout life when circulating hormones “activate” the previously organized neural circuits and biological systems. These effects:

• Are typically reversible and depend on current hormone levels
• Trigger the expression of behaviors and responses for which the organism was organized during development
• Can be turned on and off as hormone levels fluctuate
• Include effects on sexual behavior, aggression, cognitive patterns, and other sex-typed behaviors

Application to Sex and Gender Development

This framework helps explain several aspects of sex and gender development:

Typical Development: Prenatal testosterone organizes male-typical brain patterns, which are later activated by pubertal and adult testosterone to produce masculine behaviors and characteristics.

prenatal effects of hormones:

During embryonic development, sex hormones (primarily testosterone, estradiol, and anti-Müllerian hormone) affect several key brain regions that influence later behavior and physiology:

Hypothalamus – This is the most extensively studied region. Sex hormones organize areas like the preoptic area, which is crucial for reproductive behavior, and the arcuate nucleus, which regulates growth hormone release. The sexually dimorphic nucleus of the preoptic area (SDN-POA) shows dramatic size differences between males and females due to hormonal influences.

Amygdala – Particularly the medial amygdala, which processes social and sexual stimuli. Hormonal exposure during development affects both the size and connectivity patterns of this region.

Hippocampus – While traditionally associated with memory, the hippocampus also shows sex differences in structure and function that trace back to developmental hormone exposure, affecting spatial learning and stress responses.

Bed nucleus of the stria terminalis (BNST) – This region shows pronounced sexual dimorphism and plays important roles in anxiety, stress responses, and reproductive behaviors.

Cerebral cortex – Several cortical areas show subtle but measurable differences, particularly in regions involved in language processing and visuospatial abilities.

Brainstem nuclei – Areas controlling autonomic functions and some motor behaviors also show hormone-dependent sexual differentiation.

The organizational effects of these hormones typically occur during critical periods in prenatal development (and sometimes early postnatal life) and create permanent structural and functional differences. These early hormonal influences lay the groundwork for later activational effects of hormones throughout life.

The timing and concentration of hormone exposure can significantly influence which regions are affected and to what degree, making this a highly regulated developmental process.

during puberty:

During puberty, sex hormones have profound effects on brain development, with some regions showing particularly dramatic changes:

Prefrontal Cortex – This region undergoes extensive remodeling during puberty, with hormones influencing synaptic pruning and myelination. The prefrontal cortex is crucial for executive function, decision-making, and impulse control, which explains why these abilities continue developing through adolescence.

Limbic System – The amygdala and hippocampus are highly sensitive to pubertal hormones. The amygdala, which processes emotions and threat detection, shows increased reactivity during puberty, contributing to heightened emotional responses. The hippocampus continues developing, affecting memory consolidation and stress regulation.

Hypothalamus – Becomes highly active as it orchestrates pubertal changes. The hypothalamic-pituitary-gonadal axis matures, with increased sensitivity to sex hormones leading to adult reproductive function.

Striatum and Reward Circuits – Dopaminergic pathways in the striatum are significantly influenced by pubertal hormones, affecting reward-seeking behavior, risk-taking, and social motivation. This contributes to the increased novelty-seeking and peer influence characteristic of adolescence.

Corpus Callosum – The white matter tract connecting brain hemispheres continues to develop and myelinate under hormonal influence, affecting interhemispheric communication.

Social Brain Networks – Regions involved in social cognition, including parts of the temporal-parietal junction and superior temporal sulcus, show hormone-dependent changes that influence peer relationships and social behavior.

Sleep Regulation Centers – Hormonal changes affect circadian rhythm regulation in the suprachiasmatic nucleus and pineal gland, contributing to the delayed sleep phase common in adolescents.

The timing of these changes varies considerably between individuals and is closely linked to the timing of physical pubertal development. Unlike embryonic effects, many pubertal brain changes represent both organizational (permanent) and activational (reversible) effects of hormones.

The Five Stages of Puberty

Child development expert James Tanner identified five stages of puberty:

• Stage 1, starting around 7 or 8 in females and 9 or 10 in males: The brain sends signals to the body to begin producing sex hormones; few noticeable physical changes at this point
• Stage 2, starting between 9 and 11 in females and around 11 in males: Physical development begins
• Stage 3, starting after age 12 in females and around age 13 in males: Physical change become more obvious, including growth spurts
• Stage 4, starting around age 13 in females and 14 in males: Puberty is at its most intense point; this is often when males’ voices become permanently deeper and when females get their first period (although this can happen earlier)
• Stage 5, starting around 15 in both males and females: This final stage of puberty marks the culmination of a teenager’s physical development, including their full height.