Such treatment is usually restricted to the major natural androgen, testosterone, and aims to replicate physiological circulating testosterone levels and the full spectrum (including pre-receptor androgen activation) of endogenous androgen effects on tissues and recapitulating the natural history of efficacy and safety. The principal goal of androgen replacement therapy is to restore a physiologic pattern of androgen exposure to all tissues. Testosterone is used clinically at physiologic doses for androgen replacement therapy and, at typically higher doses, testosterone or synthetic androgens based on its structure are also used for pharmacologic androgen therapy. In addition, non-genomic mechanisms of androgen action involving rapid, membrane-mediated nontranscriptional processes in the cytoplasm have been described but not yet fully characterized ( 2- 4). This physiological definition of an androgen in the whole animal is now complemented by a biochemical and pharmacological definition of an androgen as a chemical that effectively competes with testosterone binding to the androgen receptor ( 1) to stimulate post-receptor functions in isolated cells or cell-free systems. The classical biological effects of androgens are primarily mediated by binding to the androgen receptor, a member of the steroid nuclear receptor superfamily encoded by a single gene located on the X chromosome, which then leads to a characteristic patterns of gene expression by regulating the transcription of an array of androgen responsive target genes. Leydig cell secretion creates a very high local concentration of testosterone in the testis as well as a steep downhill concentration gradient into the bloodstream maintaining circulating testosterone levels which exert characteristic androgenic effects on distant androgen sensitive target tissues. Testosterone has a characteristic four ring C18 steroid structure and is synthesized mainly by Leydig cells, located in the interstitium of the testis between the seminiferous tubules.
Testosterone together with its potent metabolite, dihydrotestosterone (DHT), are the principal androgens in the circulation of mature male mammals. An androgen, or male sex hormone, is defined as a substance capable of developing and maintaining masculine characteristics in reproductive tissues (notably the genital tract, secondary sexual characteristics, and fertility) and contributing to the anabolic status of somatic tissues.
0 kommentar(er)
