New Study Looks at the Effects of Aging on Testosterone in the Brain

It is well-known that as males age, testosterone levels in their blood decrease and their cognitive function declines. Testosterone is a type of hormone known as an androgen which functions by binding to an androgen receptor. Androgens play important roles in cognition, which means it’s possible that age-related declines in testosterone contribute to changes in cognition as males age.

Until now, studies in this area of research have focused on the hypothalamus and hippocampus, parts of the brain that aren’t as heavily involved in higher-order cognition. A new study published in the journal Hormones and Behavior by Drs. Kiran Soma and Stan Floresco looks at another area of the brain.

“To our knowledge, this was one of the first studies that looked at the effects of age on androgen receptors in the prefrontal cortex,” says Katelyn Low (pictured), first author of the paper and a previous Master’s student in Dr. Soma’s lab. “The prefrontal cortex controls executive function and is an area of the brain that’s really important for decision making, flexible thinking, and coordinating complex behaviours that are used on a daily basis and that we know are impacted by aging.”

Low studied the effects of aging in male rats by comparing old rats (22 months old) to young rats (5 months old). She first confirmed what was already known to be true—younger rats had higher levels of testosterone in their blood than older rats. She then used a method called “the Palkovits punch”, where a core-like tool is used to punch out a very small region of brain tissue in order to carefully measure the amount of testosterone found in that tissue. In addition, she used a novel immunohistochemical protocol that she developed, where an antibody binds androgen receptors in tissue sections, to determine where in the brain these androgen receptors exist.  

Low found testosterone declined with age in all of the brain tissues she examined except for one. With respect to androgen receptors, there were some parts of the brain where the number of receptors declined with age, and other areas where there were no significant declines. 

Several aspects of these findings are exciting. For starters, it wasn’t previously well-established that the prefrontal cortex contains so many androgen receptors. Second, it provides a clue that both testosterone and androgen receptors might be mediating changes in behavior and cognitive ability as males age, seeing as there was a drop in testosterone and androgen receptors in older male rats in parts of the brain important for executive function.

This research also raises the possibility that some areas of the brain have the capacity to buffer themselves against drops in testosterone in the blood by simply making their own. 

“We’ve started to learn that the brain can make its own testosterone—it’s not just getting testosterone from the blood,” says Dr. Soma. “What this opens up is the possibility that a drop in testosterone in the blood might mean no drop or a smaller drop in testosterone in some parts of the brain because they can regulate local testosterone levels independently of what’s in the blood.”

“We haven’t shown that directly here, but we see some areas where there’s no change in testosterone with aging, so that’s suggestive. Related to that, in all the different brain regions we look at, the levels of testosterone were higher than the levels in the blood, so that’s another piece of evidence that these parts of the brain might be making their own testosterone.”

This work is helping researchers gain a better understanding of how testosterone affects males as they get older and the potential implications this has for age-related declines in executive function. Drs. Soma and Floresco recently received a five-year Project Grant from CIHR to continue looking at the roles of testosterone in the prefrontal cortex and executive function.