Androgens

-    Role in males similar to the of estrogens in females

  - development of male sexual characteristics

  - stimulating protein synthesis, growth of bones

  - cell differenciation,    spermatogenesis

  - male type of behaviour



                                             Androgens

-    Endogenous ligands – androgen hormones

-    testosterone

-    dihydrotestosterone (DHT)

-    androstanediol

-    dehydroepiandrosterone

-    androstenedione



                                    Hypothalamo-pituitary axis

-    Regulation of testosterone synthesis

-    Hypothalamus – Gonadotropin releasing hormone

-    Pituitary – folicle stimulating and luteineising hormone

                                    Hypothalamo-pituitary axis

- Folicle stimulating hormone

- Stimulates synthesis of    androgen binding proteins   and spermatogenesis in    Sertoli cells
(testis)

- Luteineizing hormone

- Stimulates testosterone    production in Leydig cells

                                           Testosterone

-    synthetized in testis (Leydig cells)

-    in lesser extent in adrenals

                                        Dihydrotestosterone

-    The most important derivative of testosterone

-    Formed extratesticulary from testosterone

-    5a-reductase

                                        Dihydrotestosterone

-    In several tissues (seminal vesicles, prostate, skin) higher affinity to androgen receptor
than testosterone

-    Daily production 5-10% of testosterone

                                        Mechanism of action

                                           Mechanisms of
                                  androgen signalling disruption

                           Mechanisms of androgen signalling disruption

                           Mechanisms of androgen signalling disruption

                           Mechanisms of androgen signalling disruption

                           Mechanisms of androgen signalling disruption

                           Mechanisms of androgen signalling disruption

                             Effects of male exposure to antiandrogens

                             Effects of male exposure to antiandrogens

                                      AR-binding - potencies
                                     (Ref: DHT EC50 ~ 0.1 uM)

                                     Antiandrogenic compounds

                               In vivo antiandrogenicity assessment

                                             In vitro
                                   antiandrogenicity assessment

                               In vitro antiandrogenicity assessment

                                      AR-binding - potencies
                                 (Ref: DHT EC50 ~ 0.1 uM = 100nM)

                               In vitro antiandrogenicity assessment

                               In vitro antiandrogenicity assessment