Androgens and Estrogens in the Human Nervous System

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Reproductive hormones play many important roles in the central nervous system (CNS). During prenatal or early postnatal development, testosterone (or its metabolites) brings about the masculinization and defeminization of brain systems that express receptors for the hormones, permanently altering structural details of brain organization at those sites. Hormones such as estradiol, a form of estrogen, also play important roles in the adult CNS where they serve as potent neuromodulators in several neurochemical systems. The fundamental principles that govern these actions of steroid hormones have been derived mostly from studies of nonhuman species. Much less is known about the roles of these hormones in the brains of humans and other primates. However, evidence increasingly supports a regulatory role for reproductive steroids in a range of cognitive, behavioural, appetitive, and affective functions, as well as hormonal dysregulation in several psychiatric conditions and with brain aging. Research in my lab utilizes a wide range of different methods to investigate the effects of reproductive steroids in the human CNS, including neuropsychological studies of healthy people and people who have endocrine disorders, structural and functional neuroimaging, genotyping, and studies of the CNS correlates of naturally-occurring variations in steroid concentrations. We are assisted in our work by an on-site laboratory that specializes in the quantification of steroid hormones in human saliva using cutting-edge enzyme immunoassays and radioisotopic methods. Over the next 5 years, we plan to study the effects of testosterone and estradiol on several cognitive functions, especially working memory and mental rotation (a type of cognitive processing evoked when we analyze spatial positional information from the external environment). Specifically, we will test the frontal lobe hypothesis, which posits that estradiol acts on the human prefrontal cortex (PFC) and the cognitive functions it serves. Secondly, we will use biological markers of androgen activity and direct quantification of adult hormone concentrations to clarify the timing and mechanisms by which testosterone influences mental rotation and other spatial functions. Collectively, these two lines of research will help to shed new light on the timing and sites of activity of reproductive steroids in the human nervous system.