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Chapter: Modern Pharmacology with Clinical Applications: Androgens, Antiandrogens, and Anabolic Steroids

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Androgen: Mechanism of Action

Given the wide spectrum of androgen actions, it is rea-sonable to expect the intracellular processes mediating these diverse effects to vary among target tissues.

MECHANISM OF ACTION

 

Given the wide spectrum of androgen actions, it is rea-sonable to expect the intracellular processes mediating these diverse effects to vary among target tissues. The currently accepted hypothesis of androgen action in male sex accessory organs is depicted in Fig. 63.4. Testosterone diffuses from the blood across the plasma membrane of the sex accessory organ cell, where it is rapidly metabolized to DHT and androstanediol. In many sex accessory organs, DHT, rather than testos-terone, is the primary intracellular androgen and is more potent than testosterone. Once formed, DHT preferen-tially binds to a receptor protein in the nucleus. This DHT–receptor complex is subsequently activated and binds to proteins on the nuclear matrix. Following this interaction, RNA synthesis results in enhanced protein synthesis and cellular metabolism. If sufficient andro-gen stimulation occurs, DNA synthesis and cellular di-vision begin.

 

Non-sex accessory tissues also are targets for the protein anabolic actions of androgens. These tissues possess lower levels of endogenous hormone, minimal 5 -reductase activity, and lower concentrations of spe-cific androgen receptors. The protein anabolic actions are probably mediated by an interaction with the an-drogen receptor.

 

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