The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues

By A. Arnold. Hormones and Behavior, 2009

605 citations recorded by the source corpus.

The 1959 publication of the paper by Phoenix et al. was a major turning point in the study of sexual differentiation of the brain. That study showed that sex differences in behavior, and by extension in the brain, were permanently sexually differentiated by testosterone, a testicular secretion, during an early critical period of development. The study placed the brain together in a class with other major sexually dimorphic tissues (external genitalia and genital tracts), and proposed an integrated hormonal theory of sexual differentiation for all of these non-gonadal tissues. Since 1959, the organizational-activational theory has been amended but survives as a central concept that explains many sex differences in phenotype, in diverse tissues and at all levels of analysis from the molecular to the behavioral. In the last two decades, however, sex differences have been found that are not explained by such gonadal hormonal effects, but rather because of the primary action of genes encoded on the sex chromosomes. To integrate the classic organizational and activational effects with the more recently discovered sex chromosome effects, we propose a unified theory of sexual differentiation that applies to all mammalian tissues.

Subfields: Gender Studies, Genetics, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/cf66389353afbae1b24c1cf5bc8fffc6937bb42e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Gender Studies

In Genetics

In Public Health, Environmental and Occupational Health

Citations in the corpus

Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. (2009, neutral): “Subsequent to gonadal differentiation, the different types and levels of hormones produced by the testes and ovaries dictate the differentiation of most secondary sexual characteristics (Wilhelm and Koopman, 2006), others being dependent on the direct action of Y- and X-linked genes (Arnold, 2009).”
Sex Bias in Neuroscience and Biomedical Research (2010, neutral): “Sex differences are, in any case, incompletely explained by actions of sex hormones (Cahill, 2006; Arnold, 2009).”
Sex differences in anxiety and depression clinical perspectives (2014, background): “, 2013), organizational effects of gonadal steroid exposure during development, and activational effects of reproductive hormone exposure throughout the lifespan (Arnold, 2009; McCarthy et al., 2012).”
Reframing sexual differentiation of the brain (2011, background): “This iconic study provided the conceptual framework for discriminating two types of sex-specific action of gonadal steroid hormones: organizational and activationa”
Mechanistic Pathways of Sex Differences in Cardiovascular Disease. (2017, background): “On the other hand, sex hormones may also induce longer lasting effects, such as changes in DNA structure and chromatin remodeling, which are the socalled organizational effects (8).”