IS MALE BRAIN DIFFERENT FROM FEMALE BRAIN?

In 1959, exactly 50 years ago, was published a paper by Phoenix, Goy, Gerall and Young entitled "Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig". Before the publication of this paper, it was widely accepted that hormones do act upon brain. However, the general thought was that hormones, especially sex steroid hormones, directly activate certain brain areas when needed, i.e. at the time of mating, parental care etc. In contrast to this thought, Phoenix and colleagues for the very first time proposed that hormone action in neonatal period could also permanently alter brain structure, and thus influence differences in behavior long after exposure to sex steroid hormones. The study of Phoenix and colleagues was therefore revolutionary, and as such, had many opponents at that time. Even the authors themselves were very cautious in their phrasing, never directly claiming that hormones could alter brain structure but rather even in the title used the words "tissues mediating mating behavior" instead of brain or central nervous system. Furthermore, as with many such revolutionary studies, study by Phoenix and colleagues left more questions unanswered than it did answer. The authors did not and could not know at that time exactly where and how do steroid hormones act in the brain, they did not know whether observed effects in their study arose from the direct action of testosterone or perhaps from some testosterone metabolite. In half the century since the publication of this seminal study, hundreds of papers have been published, confirming initial finding of Phoenix and colleagues, and these papers have provided answers to many questions raised by the authors. Today we know that at least in rodents, it is testosterone metabolite estradiol that masculinizes the brain. We know that brain structure could be altered by hormones in different periods including puberty and probably even in adult life. We know many locations in the brain where sex steroid hormones act to cause permanent structural changes. Nevertheless, the study of Phoenix, Goy, Gerall and Young still stands strong even after 50 years, confirming the revolutionary importance of their finding.