It has been noted that the main cause of
the pattern baldness or the balding in
men is a combination of genetic predisposition
and androgens that are sufficiently circulated
in the human system. The stance of genetic
predisposition on pattern baldness remains
debatable on the areas of genetics since the
genes that cause pattern baldness are
still unmarked. Although the advancement of
the study of alopecia in men is nearing its
conclusion, the reason for alopecia in women
remains vague.
The current theory widely pursued by researches
nowadays is that the same genes are responsible
for the production of androgen, androgen conversion
to dihydrotestosterone (DHT), the activity
of the androgen receptor, and the cause of
alopecia. The importance of understanding
the genetic signature that triggers alopecia
lay in the potential treatment modules that
can be devised once the mechanism is fully
understood.
Is Androgenetic Alopecia an Autosomal Dominant
Disorder?
Non-sex determining chromosomes are called
autosomal chromosomes. An autosomal dominant
gene is one of the autosomal chromosomes in
our genetic make up. Since these autosomal
genes are dominant, these genes only need
to exist in the chromosomes of one of the
parent in order to cause diseases. In the
study of alopecia, it was generally assumed
that a person inherited baldness from the
maternal grandfather in the mode of inheritance.
However, the mode of inheritance was well
documented in the science as autosomal dominant,
implying that the inheritance of only one
autosomal gene can be a full blown genetic
predisposition.
A study in 1916 by Dorothy Osborn led to
the proposition that balding in men and in
women is due to a single gene with two alleles,
B (balding) and b (non-balding). She suggested
that balding in men occurs whichever combination
of the alleles present, that is whether the
alleles are homozygous/same (BB) or heterozygous
(Bb). Balding in women only occurs when these
alleles are homozygous. Simply put, a single
autosomal gene, termed “B,” could
account for genetic predisposition to baldness,
acting in an autosomal dominant fashion in
men and in an autosomal recessive manner in
women. In simpler words, men are predisposed
to baldness if they inherit either “BB” or “Bb”;
women are only predisposed if they inherit “BB.”
The Polygenic Hypothesis
A study in 1984 done by Kuster and Happle
re-evaluated the inheritance of pattern baldness. They found out that there is a need
for a more complex mode of inheritance needed
for pattern baldness to occur. A polygenic
trait is a trait controlled by many genes
and whose trait is the summary of the values
of each individual genes, defining a degree
with which the traits are expressed.
The authors argued that a Gaussian curve
of normal distribution that represents the
full range of phenotypes -from fully developed
baldness to no hair loss at all – was
followed by the pattern baldness distribution.
In addition, Kuster and Happle argued that
it would be highly improbable for the hereditary
traits to be determined by a single gene with
the low value of 0.1 percent. Along with this,
there is much difficulty in determining the
exact figure of men with alopecia although
an estimate runs of 40% to 60% which further
supports the pervasive mode of inheritance.
Father-to-Son Transmission
Advances in the research for alopecia suggests
that the mode of inheritance for pattern baldness involves a very complex process which
engage many genes that could involve a gene
or genes transmitted from father to son. Sexual
dimorphism in the androgen-estrogen balance
modulates the phenotypic expression of pattern baldness. However, one scientist, Hoffman,
argued against this since the androgen receptor
gene is located on the X-chromosome, which
does not explain the father-to-son inheritance.
Androgen Receptor
The main function of the androgen receptor
is to regulate the response of the androgen.
Some recent researchers believe that the gene
encoding in the androgen receptor possibly
plays a role in the regulation of androgen
potency that is available in their hair follicles – which
could be a factor in the predisposition of
pattern baldness. However, the same suggestion
offered by Hoffman hinders the advancement
of this thought since the androgen receptor
gene is located on the X-chromosome.
Nonetheless, it is not impossible for a gene
on the X chromosome to be involved in a polygenic
predisposition. Researches propose the idea
of a gene on the X chromosome causes an increase
in androgen receptor expression and increase
in potent androgen dihydrotestosterone (DHT).
DHT is also assumed to cause shortening of
the anagen phase, production of progressively
finer pseudo-vellus hairs, and the cause of
the miniaturization of the follicles, at the
same time decreasing the level of the enzyme
that converts androgens to estrogens, aromatase,
that could be detected in balding scalps.
Polycystic Ovary Syndrome and Female Pattern
Baldness
Sex hormone binding globulin (SHBG) binds
to testosterone, making the testosterone unable
to convert androgens to dihydrotestosterone
(DHT). The hypersecretion of the androgen
hormones and the below normal production of
sex hormone binding globulin (SHBG) indicates
a Polycystic Ovary Syndrome. Once a person
has Polycystic Ovary Syndrome, the insulin
levels are increased, affecting the production
of hormones and SHBG. Researches suggest that
a single gene causes the human body’s
vulnerability to Polycystic Ovary Syndrome
and the same gene may affect the production
and the effects of androgen on the body. This
gene that causes Polycystic Ovary Syndrome
on women, when passed down from the man’s
side of the family could be a possible culprit
to the balding in women.
However, not every woman with Polycystic
Ovary Syndrome develops pattern baldness.
Estrogen is an indirect antagonist of testosterone,
and the high levels of estrogen in the syndrome
may block the androgen activity to some
degree.