Androgens are key regulators of male sexual differentiation and development of a normal male phenotype. In the adult they are required for maintenance and function of male genital organs and spermatogenesis. In addition, they are involved in a large number of physiological processes such as stimulating muscle and hair growth, bone development, erythropoiesis as well as controlling male psychosocial behavior. The two main androgens in the human body are testosterone and dihydrotestosterone, the 5a-reduced derivative of testosterone. Each of them has its distinct role and target tissues. During development, testosterone produced in the testis triggers the development of the Wolffian duct structures which results in the development of the seminal vesicles, vas deferens and urethra, whereas dihy-drotestosterone, synthesized in the periphery through the action of the enzyme 5a-reductase, is crucial for development of external genitalia and the prostate from the urogenital sinus.

At the cellular level, androgen action is mediated by a high affinity receptor, the androgen receptor (AR) that functions as a ligand-activated transcription factor. This receptor is a member of the large superfamily of ligand-inducible transcription factors that share the structural and functional organization in three domains (transactivation, DNA-binding and ligand-binding domains). Binding of androgens induces a cascade of activation steps that finally result in a transcriptionally active AR capable of regulating the transcription of genes by binding to target sequences in the chromatin, termed androgen response elements.

The gene encoding the AR is located on the long arm of the X-chromosome close to the centromere region. The structural organization into 8 exons is essentially identical to those of the genes encoding other steroid receptors. Due to the sex chromosomal inheritance trait of the AR gene, AR malfunction affects males whereas females transmit genetic alterations to the next generation. Three diseases associated with AR defects are: 1) Male pseudohermaphroditism due to AR abnormalities causing complete or partial androgen insensitivity of target tissues in genetic and gonadal males. This is the most frequent cause of male sex ambiguity, and depending on the severity of the defect, the clinical symptoms span a wide spectrum from a female phenotype to patients with partial disorders and phenotypically normal males with infertility. 2) Escape from hormone ablation therapy in prostatic carcinoma is associated with a number of AR alterations that contribute to the development of hormone-insensitive tumor cells. 3) Spinal and bulbar muscular atrophy, a disease associated with a pathological AR function that is characterized by late onset, progressive weakening of skeletal muscles and impairment of motoneuron function.

100 Pregnancy Tips

100 Pregnancy Tips

Prior to planning pregnancy, you should learn more about the things involved in getting pregnant. It involves carrying a baby inside you for nine months, caring for a child for a number of years, and many more. Consider these things, so that you can properly assess if you are ready for pregnancy. Get all these very important tips about pregnancy that you need to know.

Get My Free Ebook

Post a comment