Sexual differentiation of brain and other tissues: Five questions for the next 50 years

• Published in: Hormones and behavior 2020-04, Vol.120, p.104691-104691, Article 104691
• Main Author: Arnold, Arthur P.
• Format: Article
• Language: English
• Subjects: Animals; Biomedical Research - history; Biomedical Research - trends; Brain - embryology; Compensation; Embryonic Development - physiology; Female; History, 20th Century; History, 21st Century; Humans; Male; Models, Animal; Neuroendocrinology - history; Neuroendocrinology - trends; Phenotype; Sex Characteristics; Sex chromosomes; Sex differences; Sex Differentiation - genetics; Sex Differentiation - physiology; Sexual differentiation; X chromosome; Y chromosome
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1016/j.yhbeh.2020.104691

This paper is part of the celebration of the 50th anniversary of founding of the journal Hormones and Behavior, the official journal of the Society for Behavioral Neuroendocrinology. All sex differences in phenotypic development stem from the sexual imbalance in X and Y chromosomes, which are the only known differences in XX and XY zygotes. The sex chromosome genes act within cells to cause differences in phenotypes of XX and XY cells throughout the body. In the gonad, they determine the type of gonad, leading to differences in secretion of testicular vs. ovarian hormones, which cause further sex differences in tissue function. These current ideas of sexual differentiation are briefly contrasted with a hormones-only view of sexual differentiation of the last century. The multiple, independent action of diverse sex-biasing agents means that sex-biased factors can be synergistic, increasing sex differences, or compensatory, making the two sexes more equal. Several animal models have been fruitful in demonstrating sex chromosome effects, and interactions with gonadal hormones. MRI studies of human brains demonstrate variation in brain structure associated with both differences in gonadal hormones, and in the number of X and Y chromosomes. Five unanswered questions are posed as a challenge to future investigators to improve understanding of sexual differentiation throughout the body. •Proximate sex-biasing factors include gonadal hormones and sex chromosome genes.•Sex-biasing factors can be synergistic or have opposite actions, making the two sexes more or less similar.•Animal models and MRI studies of human brain support these ideas.•Five unanswered questions are posed as a challenge for future study of sexual differentiation throughout the body.