ABSTRACT
Only a portion of human sexual development is understood at the molecular level. It is reliant on genetic regulation, which is mostly brought about by changes in the sex chromosomes between males and females. This results in the development of the gonads, after which hormone action regulates the differentiation of the apparent phenotype. Sex steroids may cause both long-term and transient effects. Testosterone, together with its bioactive metabolites dihydrotestosterone and estradiol, controls the emergence and upkeep of male sexual differentiation as well as the development of the distinctive traits of adult masculinity. At different stages of life, androgen-action defects result in recognizable clinical characteristics. Their organizational traits involve genetic control of downstream genes to produce long-lasting phenotypic alterations. Androgens play a major role in this, operating through a single androgen receptor, in the differentiation of male internal and external genitalia, as well as other sexual organs and general body composition. The pathophysiology of abnormalities in androgen activity is obtained from a description of the biochemistry and physiology of androgen action. The pharmacology of testosterone and its applications to both pharmacological androgen therapies based on either testosterone or synthetic androgens are described, as well as replacement therapy for pathological hypogonadism. The androgen receptor is a nuclear transcription factor that controls the DNA transcription of certain target genes, hence tightly controlling development and growth. The androgen receptor works in tandem with various metabolites and a variety of cofactors to modulate the cellular response, which then permanently changes the phenotype of any given individual. This specificity of androgen action appears to be a strictly time-controlled process. There must be a particular “androgen response index” suggested for each cell that androgens program.
