By Gus G. Sentementes, The Baltimore Sun
5:07 PM EDT, October 5, 2012
Aging baby boomers are increasingly turning to testosterone prescriptions in a bid to stay healthy and boost their vitality. But the therapy has some health risks for men.
Recently, scientists at the Johns Hopkins Bloomberg School of Public Health have been exploring how stem cells can be used to regenerate testosterone in aging men, without their having to resort to testosterone injections.
"We're trying to understand whether you can prevent [diminishing testosterone], whether you can reverse that," said Dr. Barry Zirkin, a Hopkins researchers who has co-developed a new way to activate stem cells in the testes that, in turn, form the cells that produce testosterone.
The demand for testosterone therapy is high. Major pharmaceutical companies are pitching their products to an eager and aging male population who, some say, are seeking the proverbial "fountain of youth." The global market for testosterone replacement therapy is expected over the next five years, to reach $5 billion, according to a report this year from Global Industry Analysts Inc.
Scientists have been exploring the effects of diminishing testosterone for decades, and how to combat it. But conclusive findings have been out of reach. The National Institute of Aging has an ongoing "Testosterone Trial" — a multi-year clinical study it began two years ago to determine how low levels of the hormone affect men who are 65 or older.
Can the human body itself be used to regenerate low testosterone levels in men? The Hopkins scientists are in the early stages of studying this possibility.
Zirkin and Dr. Haolin Chen, both professors of biochemistry and molecular biology, have worked together for years to attempt to understand how testosterone is produced in the testes. Zirkin, who is head of the division of reproductive biology at Hopkins, said men can produce a third less testosterone by the time they reach 80 years old.
Zirkin said they studied whether the pituitary gland in the brain signaled the testes with a particular hormone to slow down testosterone production as men age. So far, they've learned that doesn't happen.
"What that means is the problem is in the testicle itself, and not in the brain," Zirkin said.
In a study the pair recently published in the journal Endocrinology, the scientists laid out the two approaches they developed in their experiments with rats that yielded promising new ways to regenerate the cells that make testosterone.
In the first approach, the scientists isolated stem cells in the testes and cultured them to grow Leydig cells, which in turn produced testosterone.
But in lab experiments on brown rats, Zirkin and Chen discovered that they can kill off the aged Leydig cells, which aren't producing as much testosterone, and activate the stem cells to produce new, healthier cells that can start producing testosterone again.
"The stem cells have not aged," Zirkin said. "We're trying to understand what they are."
Leydig cells don't die. But they age and become decrepit, and less useful, Zirkin said.
In the second approach, the researchers isolated and cultured two major components of the testes, known as the seminiferous tubules and the interstitium. Sperm is made inside the tubules, while the Leydig cells, which make testosterone, are located just outside the tubules.
The scientists discovered they could produce testosterone from stem cells located on the tubules' surfaces.
About the study
What: Hopkins researchers develop ways to study stem cells that can be cultured to create so-called Leydig cells, which in turn produce testosterone in adult male testes.
Who: Co-authors Dr. Barry Zirkin and Dr. Haolin Chen, professors in the biochemistry and molecular biology department.
Significance: Many aging men are turning to testosterone injections to improve their cognition and vitality. The researchers are exploring how the body's own cells can be used to create more of the hormone.
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