Testis determining factor

Testis determining factor
Structure of the SRY protein, which contains the testis determining factor
Identifiers
Symbol	?
HGNC	11364
OMIM	480000
PDB	1J46

The testis determining factor (TDF), also known as sex-determining region Y (SRY), is a protein encoded by the SRY gene on the Y chromosome. It is a critical factor in the initiation of male sex determination in humans and other mammals. The presence of TDF triggers the development of the undifferentiated gonadal tissue into testes, which subsequently leads to the production of male hormones and the development of male physical characteristics.

Structure and Function

The testis determining factor is a transcription factor, which means it binds to specific DNA sequences to regulate the expression of other genes. The SRY protein contains a high-mobility group (HMG) box domain, which is responsible for its DNA-binding activity. This domain allows the SRY protein to bend DNA, facilitating the interaction of other transcription factors and the activation of downstream genes involved in testis development.

The primary role of TDF is to initiate the differentiation of the bipotential gonadal ridge into testes. This process involves the upregulation of several genes, including SOX9, which is crucial for testis formation. The expression of SOX9 leads to the development of Sertoli cells, which are essential for testis cord formation and the subsequent production of anti-Müllerian hormone (AMH). AMH causes the regression of the Müllerian ducts, preventing the development of female reproductive structures.

Genetic and Clinical Implications

Mutations or deletions in the SRY gene can lead to disorders of sex development (DSDs). One such condition is Swyer syndrome, also known as 46,XY gonadal dysgenesis, where individuals with a typically male karyotype (46,XY) develop as females due to the absence or dysfunction of the SRY protein. Conversely, translocation of the SRY gene to an X chromosome can result in 46,XX testicular disorder, where individuals with a typically female karyotype develop male characteristics.

Evolutionary Perspective

The SRY gene is believed to have evolved from a gene duplication event of the SOX3 gene on the X chromosome. This evolutionary event allowed the Y chromosome to acquire a gene that could initiate male sex determination, leading to the differentiation of the sexes in mammals. The presence of SRY and its role in sex determination is a key factor in the evolution of sexual dimorphism in mammals.

Research and Future Directions

Ongoing research aims to further elucidate the molecular mechanisms by which SRY and its downstream targets regulate sex determination. Understanding these pathways is crucial for developing therapeutic interventions for DSDs and for advancing knowledge in reproductive biology and endocrinology.

Also see

• SRY gene
• Sex determination system
• Disorders of sex development
• SOX9
• Anti-Müllerian hormone