Androgenic Steroids Overall Organization of the Topic Overall mechanism of steroid hormone action Structure of male sex hormones - Testosterone, androstendione, and 5a-dihydrotestosterone Nomenclature of androgenic steroids Physiological activities - Androgenic and anabolic activities Biosynthesis and metabolism of testosterone Structure activity relationships - Generalizations Androgen antagonists - Finasteride, danazol, bicalutamide and flutamide 11/27/2018 MEDC 603 Steroids

Steroid Hormones Overall Mechanism of Steroid Hormone Action (intracellular) (intranuclear) proteins Intracellular effects extracellular effects transcription translation dimerization DNA (extracellular) 11/27/2018 MEDC 603 Steroids

Androgenic Steroids Structure and Nomenclature Testosterone Androstendione (Andro) (17b-hydroxy-androst-4-en-3-one) 3D-structure (androst-4-en-3,17-dione) 5a-Dihydro-testosterone (17b-hydroxy-5b-androstan-3-one) 3D-structure 11/27/2018 MEDC 603 Steroids

Androgenic Steroids – Physiological Activities Primarily two activities – Androgenic and Anabolic Androgenic Activity Growth and development of male sex organs Important for male sex drive and performance Development of secondary sexual characteristics Important role in spermatogenesis Anabolic Activity Development of muscle mass Reverse catabolic or tissue-depleting processes 11/27/2018 MEDC 603 Steroids

Androgenic Steroids - Physiological Activities Andro is available over the counter!! 11/27/2018 MEDC 603 Steroids

Biosynthesis and Metabolism of Testosterone Cholesterol Pregnenolone Testosterone Other metabolites 5a-DHT Androstendione 11/27/2018 MEDC 603 Steroids

Structure Activity Relationships in Androgens Anabolic Androgenic Testosterone 1 1 (injectable) Testosterone 1 1 esters (injectable) R = COCH2CH3 propionate = CO(CH2)5CH3 enanthate = COCH2CH2(C5H9) cypionate 11/27/2018 MEDC 603 Steroids

Structure Activity Relationships in Androgens Anabolic Androgenic 17a-methyl Testosterone 1 1 (oral) Fluoxymesterone 1 1 (oral) 11/27/2018 MEDC 603 Steroids

Structure Activity Relationships in Androgens Anabolic Androgenic Nandrolone 2.5 1 (injectable) Oxymetholone 2.5 1 (oral) 11/27/2018 MEDC 603 Steroids

Structure Activity Relationships in Androgens Anabolic Androgenic Stanozolol 3 1 (oral) Dromostanolone 4 1 (oral) 11/27/2018 MEDC 603 Steroids

Structure Activity Relationships in Androgens Generalizations Steroid skeleton is necessary An electronegative (may not be oxygen) at 3 position is required A/B ring fusion should be either trans or presence of a double bond at 4 position Alkyl group (CH3) at 17a-position is necessary for anabolic activity Alkyl group at 17a- confers oral activity 11/27/2018 MEDC 603 Steroids

Androgens Antagonists Danazol (endometriosis) Finesteride (baldness) Bicalutamide (prostate cancer) Flutamide (prostate cancer) 11/27/2018 MEDC 603 Steroids