The Difference between the Sexes - From Biology to Behaviour

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Margaret McCarthy

University of Maryland, USA

Biography

Margaret (Peg) McCarthy received a BA and MA in Biology from the University of Missouri - Columbia and a PhD from the Institute of Animal Behavior at Rutgers University, Newark NJ. She received postdoctoral training at Rockefeller University from 1989 to 1992 in the Laboratory of Dr. Donald Pfaff and one year at NIH as a National Research Council Fellow. Peg joined the faculty of the University of Maryland School of Medicine in 1993 and is currently a Professor in the Departments of Physiology and Psychiatry. She was the Director of Graduate Education for the Program in Neuroscience for three years and is currently Associate Dean with responsibility for the Graduate Program in Life Sciences which oversees the training of 400 MS and PhD students and 350 postdoctoral fellows. She has received numerous awards and recognition for her mentoring of graduate students. Dr. McCarthy has a long standing interest in the cellular mechanisms establishing sex differences in the brain. She uses a combined behavioral and mechanistic approach in the laboratory rat to understand both normal brain development and how these processes might go selectively awry in males versus females. Dr. McCarthy has published over 120 peer-reviewed manuscripts on these topics and her research has been continuously funded by the NIH since 1994. She is currently an Editor at Endocrinology and Associate Editor at the Journal of Neuroscience. She is former Associate Editor of Hormones and Behavior, past Secretary of the Society for Behavioral Neuroendocrinology, current Councilor in the Organization for the Study of Sex Differences and was named one of Maryland’s Top 100 Women in 2009.

Abstract

Establishing Sex Differences in the Brain: Lessons from Animal Models

Sex differences in the brain are predominantly established during a developmental sensitive window and are the consequence of differential exposure of males and females to steroids of gonadal origin. Research in animals has revealed distinct and active processes of brain masculinization and defeminization, both of which are the result of elevated testosterone synthesized by the testis early in development. Feminization of the brain is the default process, although recent findings implicate a later period of hormonal sensitivity that drives this developmental program as well. Steroids are potent regulators of both gene transcription and membrane initiated signaling cascades. Recent research by our group has identified multiple regionally specific unique mechanisms by which steroid hormones exert enduring organizational effects on the brain that are manifest via changes in synaptogenesis, neurogenesis, glial morphology and cell death. We have characterized unexpected roles for prostaglandins, endocannabinoids, amino acid transmitters and epigenetics. Unifying principles are that; 1) cell-to-cell communication is a key aspect of hormonally mediated sexual differentiation, resulting in entire populations of cells changing morphology in response to steroids, 2) the number of distinct and independent mechanisms involved exponentially increases the potential for individual variability in final phenotype, 3) the nature of the neuroanatomical sex differences and the mechanisms establishing those differences are categorically different in brain regions directly associated with reproductive function versus those involved in cognition and emotionality, and 4) the regional variability in mechanisms highlights the inaccuracy of referring to a “male” versus “female” brain and the need to understand that every brain is a mosaic of relative maleness and femaleness. Elucidating mechanism provides insight into the origins and functions of sex differences in the brain that are determined intrinsically by steroids and/ or genetics. Only by understanding the biological basis of sex differences can we also understand the importance of cultural and societal influences on sex and gender in humans.