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Baillieres
Clin Endocrinol Metab. 1994 Apr;8(2):405-31.
Role of 5 alpha-reductase in health and disease.
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Abstract
The mechanism of androgen action varies in different tissues, but in the
majority of androgen target tissues either testosterone or 5
alpha-dihydrotestosterone (DHT) binds to a specific androgen receptor to form a
complex that can regulate gene expression. Testosterone is metabolized to DHT
by the enzyme 5 alpha-reductase. The autosomal recessive genetic disorder of 5
alpha-reductase deficiency has clearly shown that the requirement for DHT
formation varies with different tissues. In this syndrome genetic males contain
normal male internal structures including testes, but exhibit ambiguous or
female external genitalia at birth; at puberty they undergo partial
virilization which includes development of a male gender identity even if
brought up as females. Their development suggests that testosterone itself is
able to stimulate psychosexual behaviour, development of the embryonic wolffian
duct, muscle development, voice deepening, spermatogenesis, and axillary and
pubic hair growth; DHT seems to be essential for prostate development and
growth, the development of the external genitalia and male patterns of facial
and body hair growth or male-pattern baldness. How different hormones operate
to regulate genes via the same receptor is currently unknown, but appears to
involve cell-specific factors. The 5-alpha-reductase enzyme has proved
difficult to isolate biochemically, but recently at least two human isoenzymes
have been identified using molecular biological methods. All the various 5
alpha-reductase-deficient kindreds have been shown to have mutations in 5
alpha-reductase 2, the predominant form in the prostate. The biological role of
5 alpha-reductase 1 has not yet been ascertained, but at present it cannot be
ruled out that some of the actions ascribed to testosterone are indeed in cells
producing DHT via this enzyme. The activity of 5 alpha-reductase is also
implicated in benign prostatic hypertrophy, hirsutism and possibly male-pattern
baldness; recent evidence discounts the role of 5 alpha reductase 2 in
sebaceous glands and acne. Specific inhibitors of both enzymes are now
available and finasteride, a 5 alpha-reductase 2 inhibitor, has been used
successfully in clinical trials of benign prostatic hypertrophy. Knowledge of 5
alpha-reductase is expanding dramatically at the moment with the application of
molecular biological methods. The advent of antibodies to the isoenzymes should
herald further understanding of their biological and clinical roles.
PMID: 8092979 [PubMed - indexed for MEDLINE]
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