The inheritance of pattern baldness is complex

Male and female pattern hair loss information
 
 Genetics and inheritance of androgenetic alopecia

The genetics of androgenetic alopecia Is complex. In men, the hair loss of androgenetic alopecia is assumed to be caused by a combination of genetic predisposition and sufficient circulating androgen, but it is unclear as to whether the condition in women is the same as that in men. However, the nature of inheritance or the genetic predisposition to androgenetic alopecia remains controversial, as the exact genes causing androgenetic alopecia have not been identified yet.

The genes suspected in the involvement of androgenetic alopecia are those involved in androgen production, androgen conversion to dihydrotestosterone (DHT) and activity of the androgen receptor. Studies to identify the predisposing genes are in progress, and a breakthrough in the identification of such genes will allow a more thorough understanding of the mechanisms that cause hair loss. This breakthrough will consequently provide the foundation upon which effective treatment modules can be devised.

Is androgenetic alopecia an autosomal dominant disorder?

Although it is generally assumed that baldness in a person is inherited from the maternal grandfather, the mode of inheritance, as documented in scientific literature, is autosomal dominant, alluding that inheritance of only one autosomal gene conveys full genetic predisposition. An autosomal dominant gene is an abnormal gene on one of the autosomal (non-sex determining) chromosomes. Because it is dominant, it need only exist in the inherited chromosomes of one parent for it to cause disease.

In 1916, Dorothy Osborn proposed 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 occurs in homozygous (BB, i.e. having the same alleles at a particular gene locus on homologous chromosomes) and heterozygous (Bb, i.e. carrying a different version of that gene on each of the two corresponding chromosomes) men; but only in homozygous women. She therefore concluded that 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

In 1984, Kuster and Happle re-evaluated the inheritance of androgenetic alopecia and argued that there is a more complex polygenic mode of inheritance in androgenetic alopecia. A polygenic trait is one where it is thought that many genes control a trait, and it is the 'quantitative sum' of the 'values' of those genes that define the degree to which the trait is expressed.

Kuster and Happle argued that the distribution of androgenetic alopecia follows a normal distribution curve representing the full range of phenotypes, from no evidence of hair loss to fully developed baldness. In addition, Kuster and Happle point out that hereditary traits determined by a single gene rarely occur with a frequency greater than 1:1000. Although the exact frequency of androgenetic alopecia is difficult to ascertain, it has been estimated to be between 40% and 60% in men, further supporting a more pervasive mode of inheritance.

Father to son transmission

Recent studies show that the mode of inheritance of predisposition to androgenetic alopecia is likely to be complex, probably involving several genes, and may involve a gene (or genes) that are transmitted from father to son. The phenotypic expression of androgenetic alopecia is further modulated by the sexual dimorphism in the androgen/ estrogen balance. However, Hoffman argues that the androgen receptor gene is located on the X chromosome and does not explain father to son inheritance.

Androgen receptor

Response to androgen in the form of gene regulation is moderated by the androgen receptor. Some researchers are of the belief that it is possible that the gene encoding the androgen receptor plays a role in regulating the potency of androgen available to the hair follicle – thus may be a factor involved in androgenetic alopecia predisposition. However, the androgen receptor is located on the X chromosome, which does not help to explain the father-to-son transmission of androgenetic alopecia purported by some.

Although it is not impossible for a gene on the X chromosome to be involved in a polygenic predisposition, it is perhaps more likely that a mechanism that causes an increase in the potent androgen dihydrotestosterone (DHT), also causes an increase in androgen receptor expression. DHT is believed to shorten the growth, or anagen, phase of the hair cycle, causing miniaturization of the follicles, and producing progressively finer or pseudo vellus hairs. DHT, increased levels of the androgen receptor and decreased levels of aromatase, the enzyme that converts androgens to estrogens, have been detected in balding scalp.

Polycystic ovary syndrome and female pattern baldness

Polycystic Ovary Syndrome (PCOS) is characterized by hypersecretion of androgen hormones and below normal production of sex hormone binding globulin (SHBG). SHBG binds to testosterone and renders it unavailable for conversion to dihydrotestosterone (DHT). Additionally, Polycystic Ovary Syndrome involves increased insulin levels, which has an affect on hormone production and SHBG. Research also suggests that vulnerability to Polycystic Ovary Syndrome is impelled by a single gene and that the gene may affect androgen production or androgen effects on the body. The gene probably causes Polycystic Ovary Syndrome in women, and when passed down the man's side of the family, causes a tendency towards early balding.

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.

Conclusion

Although the involvement of androgens in androgenetic alopecia is well established, the mode of inheritance of genetic predisposition remains a grey area. The theory that a single autosomal gene is responsible for this predisposition has been widely cited. However, it seems more likely that predisposition is determined by a number of genes in a polygenic fashion, and is modulated by the androgen / estrogen balance. It is also possible that a component of this polygenic predisposition is passed from father-to-son, and may involve the Y chromosome or genes that are capable of parental imprinting.