Mechanism of Action of Testosterone (Androgen)

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Chapter: Essential pharmacology : Androgens and Drugs for Erectile Dysfunction

Testosterone can largely be regarded as the circulating prohormone. In most target cells, the 4–5 double bond is reduced → dihydrotestosterone— which binds more avidly with the cytoplasmic receptor, and this complex is more active than testosterone-receptor complex in combining with DNA.


MECHANISM OF ACTION

 

Testosterone can largely be regarded as the circulating prohormone. In most target cells, the 4–5 double bond is reduced dihydrotestosterone— which binds more avidly with the cytoplasmic receptor, and this complex is more active than testosterone-receptor complex in combining with DNA. After combining with androgen response elements of the target genes, DNA transcription is enhanced and effects are expressed through modification of protein synthesis.

 

The 5α-reductase enzyme exists in two isoforms: 5α-reductase1 and 5αreductase2. The genital skin of both sexes and urogenital tract of male contains 5α-reductase-2 which is more sensitive to inhibition by finasteride. Genetic deficiency of this isoenzyme causes male pseudo-hermaphroditism because of inability of male genitalia to produce the active hormone dihydrotestosterone from circulating testosterone. 5αreductase1 has a wider distribution in the body including non-genital skin and liver; it is less inhibited by finasteride.

 

Testosterone itself appears to be the active hormone at certain sites—foetal genital rudiments, hypothalamus/pituitary site involved in feed back regulation, erythropoietic cells and spermatogenic cells in testes.

 

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