Male vs. Female Brain Differences & How They Arise From Genes & Hormones | Dr. Nirao Shah

**Andrew Huberman** (0:00)
Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Nirao Shah. Dr. Nirao Shah is a professor of psychiatry and behavioral sciences and neurobiology at Stanford University School of Medicine. Dr. Shah is both an MD and a PhD, and his laboratory focuses on understanding the neural and hormonal mechanisms underlying sex differences in the brain. During today's episode, we discuss what is known about male and female differences in brain structure and function, and how those differences arise across development, both in utero and postnatally, that is during puberty and into adulthood. A lot of our discussion centers around testosterone and estrogen, and how both of those hormones play a profound impact on the development of both the male and female brain, but leads to different outcomes in male versus female brains. We also discuss the neural circuits that control sex behavior and aggressive behavior in both males and females, and how those are activated by different hormones. As you all know, there is immense interest and a lot of controversy around sex differences and how that relates to gender. Today's discussion centers around the biology of sex differences in the brain and body, and it will provide a very useful template for everybody in thinking about male versus female differences in behavior, in emotions, and how that intersects with gender and culture. As you'll soon see, Dr. Shah is a true expert in understanding sex differences in the brain and body and how those arise. He's also unafraid of addressing what is known and unknown about those differences and their origins. And he embraces that sex differences are one of the most impactful aspects of human biology and health. So by the end of today's episode, you will indeed have the most up to date information on this important topic. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Nirao Shah. Dr. Nirao Shah, welcome.

**Nirao Shah** (2:14)
Thank you, Andrew. Pleasure to be here.

**Andrew Huberman** (2:15)
You work on one of the most interesting topics in the entire world, which is sex differences in the brain. And the impact of hormones on the brain, on behavior. Let's start with a very straightforward question.
Are there male-female differences in terms of brain structure and function?

**Nirao Shah** (2:34)
Yes. Let me qualify that. So we work on the mouse, on the mouse brain. And we and others have identified lots of differences in structure and connections and numbers of neurons, numbers of cells in the brain. And also my own lab is focused on identifying differences in gene expression between females and males. And there are huge differences.

**Andrew Huberman** (2:53)
For the topics we're going to discuss today, I know that we're going to lean heavily on mouse data. But I think it's fair to say that because so much of those data rely on the structure and function of the hypothalamus, which you'll educate us on, how conserved is the hypothalamus between mouse and human?

**Nirao Shah** (3:11)
I would say anatomically, from an atlas, if you're just looking at atlases of humans and mice, they're very conserved. You can point to regions in the mouse brain, the ventromedial hypothalamus, for example, the VMA, which we might talk about, controls aggression and other behaviors, female sexual behavior. You can say, this is the VMA in the mouse. And you can basically pinpoint the same region of the human brain. And it's turning out to be clinically relevant as well in humans. You can do the same thing for the preoptic area, which controls maternal behaviors, preoptic male sexual behavior. And we can identify the same region in the human brain as well. So anatomically, there are very similar analogs.
In the human hypothalamus, as there are in the mouse. And this region is conserved because it controls, as you pointed out, very fundamental functions. Reproduction, aggression, taking care of young, thirst, temperature. So these tend to be conserved because you don't want to muck with the circuit that's already functioning. That's essential for survival. So you can find analogs of these structures all day from birds across vertebrates, from birds, lizards, rodents, non-human primates and humans.

**Andrew Huberman** (4:14)
I think many people lean toward the idea that humans are so different than mice and they like that idea because it somehow, I don't believe this, but I think it somehow gives them the impression that they have more degrees of freedom over their feelings and behavior than perhaps they would if we were a slave to our hypothalamus or something of that sort. But studies on the human, as you and I know, where different hypothalamic circuitries have been stimulated, reveal that you can elicit rage, you can elicit sexual desire, behavior, and on and on in a human just as you can in a mouse. Yeah.