New Study by Dr. Margaret McCarthy’s Lab Shows How Male Sex Steroids Play a Key Role in Understanding Behavioral Development

Researchers at the University of Maryland School of Medicine have discovered a mechanism for how androgens -- male sex steroids -- sculpt brain development. The research, conducted by Margaret M. McCarthy, Ph.D., Professor of Pharmacology and Chair of the Department of Pharmacology, could ultimately help researchers understand behavioral development differences between males and females.

The research, published in Neuron, discovered a mechanism for how androgens, male sex steroids, sculpt the brains of male rats to produce behavioral differences, such as more aggression and rougher play behavior. “We already knew that the brains of males and females are different and that testosterone produced during the second trimester in humans and late gestation in rodents contributes to the differences but we did not know how testosterone has these effects,” said Dr. McCarthy.

Jonathan Van Ryzin, PhD, a Postdoctoral Fellow, was lead author on this research conducted in Dr. McCarthy’s lab.

A key contributor to the differences in play behavior between males and females is a sex-based difference in the number of newborn cells in the part of the brain called the amygdala, which controls emotions and social behaviors. The research showed that males have fewer of these newborn cells, because they are actively eliminated by immune cells.

In females, the newborn cells differentiated into a type of glial cell, the most abundant type of cell in the central nervous system. In males however, testosterone increased signaling at receptors in the brain, causing immune cells to be activated. The endocannabinoids prompted the immune cells to effectively eliminate the newborn cells in males. Females rats in the study were unaffected, suggesting that the activation of the immune cells by the increased endocannabinoids in males was necessary for cell elimination. In this respect, this research shows that cannabis use, which stimulates endocannabinoids in the brain and nervous system, could impact brain development of the fetus and this impact could differ between male and female fetuses.

This study provides a mechanism for sex-based differences in social behaviors and suggests that differences in androgen and endocannabinoid signaling may contribute to individual differences in brain development and thus behavioral differences among people.

“These discoveries into brain development are critical as we work to tackle brain disorders as early in life as possible, even in pregnancy,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor.

This research was funded by NIH, Natural Sciences and Engineering Council of Canada, Canadian Institutes of Health Research, Alberta Innovates, and BranchOut Neurological Foundation.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and more than $530 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu