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Multiple Levels of Determination of Sex Differences in Brain and Behaviour

Abstract

A large number of genetic, hormonal, molecular and environmental influences, especially during certain critical periods, cooperate to determine sex differences in brain and behaviours (reviewed, 'Man & Woman: An Inside Story', Oxford, 2010). Nevertheless, it is possible to isolate specific events of relevance, using molecular techniques during brain development. We did a microarray looking for sex differences in specific brain regions during the neonatal critical period for sexual differentiation of the brain, and, in the preoptic area, found a remarkably large number of mRNA's whose levels were significantly different between neonatal males and neonatal females. Of obvious physiological importance are mRNA levels for Connexin-36, whose proteins form neuron-neuron gap junctions. Thus, of great interest are specific histone modifications associated with the Connexin-36 promoter.

Sex differences will be reported relevant to neurons important for social behaviours. Knowing mechanisms for sex differences in elementary sex behaviours, we have expanded our scope to consider the most powerful and essential brain function: generalized CNS arousal. Surprisingly, the structure of generalized arousal components is different between males and females (Weil, PNAS, 2010; Quinkert, ms submitted). Thus, sex differences in histone chemistry associated with promoters of certain arousal-related genes are being studied, using methodological approaches we have already proven successful for stress (Hunter, PNAS, 2009) and sex behaviour (Weil, SFN, 2009).

Biography

Born in Rochester, N.Y., on December 9, 1939, he received the A.B. degree magna cum laude from Harvard College in 1961 and a Ph.D. from the Massachusetts Institute of Technology in 1965. He held a National Merit Scholarship, Harvard National Scholarship, Woodrow Wilson Fellowship, MIT President's Award Fellowship, National Institutes of Health Predoctoral Fellowship and National Science Foundation Postdoctoral Fellowship. Pfaff joined The Rockefeller University in 1966 as a postdoctoral fellow. He was named assistant professor in 1969, associate professor in 1971, granted tenure in 1973 and promoted to full professor in 1978. He is a member of the U.S. National Academy of Sciences and a fellow of the American Academy of Arts and Sciences, and has received numerous scientific recognitions. He is the author of “Estrogens and Brain Function” (Springer, 1980); “Drive: Neurobiological and Molecular Mechanisms of Sexual Motivation” (MIT Press, 1999); and Brain Arousal (Harvard Univ. Press, 2006).