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Sex determination and differentiation (human)
Human sex determination refers to the processes by which an individual becomes either a male or female during development.
Additional recommended knowledge
The Jost Paradigm
Under typical circumstances, the sex of an individual will be determined and expressed through the following mechanisms:
Sex determination at the chromosome level
For the majority of individuals, sex determination is as simple as the presence or absence of a Y chromosome. Those individuals with a Y chromosome (including XXY, XXXY, etc.) will develop into males, and those without one will become female. Some individuals, however, will undergo what is referred to as primary sex reversal, whereby the X and Y chromosomes [cross over] and exchange genetic material. This relatively rare occurrence (approximately 1 in 20000 births) can lead to males with two X chromosomes and females with a Y chromosome.
Testis determining gene
During the late 1980s and early 1990s, coinciding with the mapping of the human genome, researchers began to look for the specific gene on the Y chromosome that, up until then, had been known as the testis determining factor (TDF). Through the study of individuals that underwent primary sex reversal (that is, XX males and XY females), researchers determined that the TDF must lie on the Y chromosome in a location that would permit its exchange to the X chromosome during cross over. In 1985, Dr. David C. Page published an article in Nature boldly stating that the TDF was the ZFY gene on the Y chromosome. However, Dr. MS Palmer later discovered a ZFY analogue on the X chromosome, providing evidence that ZFY was in fact not the TDF. Eventually, Dr. Peter Koopman was able to prove that the SRY gene is the TDF from studies on XX males.. The fact that SRY supports the following evidence further supports this claim:
SRY a repressor?
Recently, it has been suggested by some that the SRY gene acts as a repressor or inhibitor of another gene, “Z”, that is involved in female development. Previously, it was stated that the SRY sequence suggests the presence of a DNA binding motif. Also, the idea that SRY is a repressor is further supported by the fact that a small percentage of sex reversal cases cannot be explained by the absence of SRY and could be due to a mutation in some gene “Z” that prevents the binding of SRY and its subsequent antagonist action.
Other sex determination genes
Sex differentiation refers to the expression of phenotypic attributes specific to the sex of an individual. While gonad development is a result of the presence or absence of the sex determination gene SRY on the Y chromosome, sex differentiation is determined by the hormonal products produced by the gonads.
In the 1930s, Alfred Jost determined that the presence of testosterone was required for Wolffian duct development in the female rabbit.
Müllerian inhibiting substance
Jost also observed that while testosterone was required for Wolffian duct development, the regression of the Müllerian duct was due to another substance. This was later determined to be Müllerian inhibiting substance (MIS), a 140 kD dimeric glycoprotein that is produced by sertoli cells. MIS blocks the development of Müllerian ducts, promoting their regression.
5-alpha dihydrotestosterone (DHT)
Testosterone is converted to the more potent DHT by 5-alpha reductase. DHT is necessary to exert androgenic effects farther from the site of testosterone production, where the concentrations of testosterone are too low to have any potency. A 5-alpha reductase deficiency results in an androgen disorder characterized by female phenotype or severely undervirilized male phenotype with development of the epididymis, vas deferens, seminal vesicle, and ejaculatory duct, but also a pseudovagina.
The following disorders are caused by a malfunction in the sex determination and differentiation process:
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Sex_determination_and_differentiation_(human)". A list of authors is available in Wikipedia.|