7.14: THIS IS HOW WE DO IT: What is the cause of male-pattern baldness?
It is a rare scientist who is interested only in finding a particular answer. Most are drawn to scientific thinking because it illuminates productive ways of approaching a problem. The greatest advances in understanding often come about by exploring new approaches to old problems. And here we explore one of the oldest.
Why do men lose their hair? Conventional wisdom has long suggested that baldness in men is a trait they inherit from their mother. This hypothesis goes back to 1916, when Dorothy Osborn published the first scientific study putting forth heredity as a cause of baldness. In her paper, she took aim squarely at one of the most widely held hypotheses of the time: that the wearing of hats caused baldness due to pressure they put on blood vessels that nourish the scalp.
Can you propose how to test the “hats cause baldness” hypothesis?
Falsifiable hypotheses have the potential to be rejected. It was easy for Osborn to demonstrate that, as she put it, “the hat is not to blame.” In spite of definitive evidence against them, however, numerous equally wrong hypotheses persist today: “The hair follicles are clogged from shampoo and too much washing.” “Not enough blood is circulating around the scalp.” “Hair gels and other products are toxic.”
Are these hypotheses falsifiable? Propose how to test each of them.
What Osborn found was that it’s actually pretty difficult to study the inheritance patterns of baldness carefully. For starters, it’s very common—about 50% of men experience some balding by the age of 50, and 70% by age 70.
Why do these observations make conventional pedigree analysis difficult?
Also, because balding increases with age, it’s hard to know whether younger, non-bald men will go bald later or never at all. And it’s unclear whether all patterns of balding have the same underlying causes or should be considered different phenomena.
A modern approach. In 2005, researchers took a very modern approach to studying the inheritance of baldness. They studied in detail the DNA of 391 men—including 201 balding men—from 95 families in which at least two brothers exhibited early-onset male-pattern baldness. For comparison, they also examined the DNA of additional, unrelated men who were either under the age of 40 with male-pattern baldness or were over the age of 60 and unaffected by baldness.
The most common pattern the researchers found was that the men with male-pattern baldness were significantly more likely to share one particular stretch of DNA on their X chromosome. The unaffected men were significantly more likely to share a different sequence of DNA.
Balding men commonly shared a DNA sequence on their X chromosome. What does that tell us about whom they inherited that DNA from?
The finding that the DNA region implicated in baldness was on the X chromosome confirmed the long-standing observation that male-pattern baldness is a trait passed down to men from their mothers. Men receive their sole X chromosome from their mother and their Y chromosome from their father.
Future directions? This research resolved one long-standing debate. In the researchers’ words, “the average phenotypic resemblance should be greater between affected males and their maternal grandfathers than between affected males and their fathers.” More importantly, perhaps, it illuminated an avenue for research on the treatment of male-pattern baldness. The DNA sequence associated with male-pattern baldness, it turned out, is located within the region of a single gene—a gene already suspected to play a role in triggering baldness. The gene carries instructions for the production of androgen receptors. Androgens are male sex hormones, such as testosterone.
The DNA sequence that was found so much more frequently among individuals exhibiting male-pattern baldness was associated with higher activity of the androgen receptor gene. And although the researchers were not able to determine the exact relationship between the androgen receptor gene and male-pattern baldness, they suspect that the DNA sequence somehow increases the impact of androgens, thereby leading to hair loss. This is consistent, they noted in their paper, with the finding that castrated males—who produce almost no androgens at all—don’t go bald.
What strategies for treating male-pattern baldness do these observations suggest?
Stopping short of the one-gene = one trait conclusion. The researchers concluded that this maternally inherited allele does play a central role in the inheritance of male-pattern baldness. But they stopped short of saying that it is the only contributor to male-pattern baldness. And in a later study, they identified some autosomal genes (on chromosome 20) that contribute to a smaller, but still important, similarity between fathers and sons in patterns of male-pattern baldness.
This research increases our confidence that baldness in men is a trait they inherit from their mother. No one would say, however, that one or several genes cause male-pattern baldness. Discuss the several reasons why such a definitive assertion should not be made.
TAKE-HOME MESSAGE 7.14
Observations of male-pattern baldness within families and comparisons with unrelated individuals suggest that the baldness is caused by a sex-linked gene that codes for an androgen receptor. Males inheriting an allele—always from their mother—for higher activity of the androgen receptor gene are more likely to have male-pattern baldness than males inheriting an alternative allele.
In seeking to explain the cause of male-pattern baldness, one hypothesis is that hair gels and other hair care products are toxic. Is this a falsifiable hypothesis? Propose how to test it.