Mechanism of Action of Testosterone (Androgen)
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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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