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Hair Loss Study Abstract: 4-pregnene-3-one-20 beta-carboxaldehyde: a potent inhibitor of 17 alpha-hydroxylase/C17,20-lyase and of 5 alpha-reductase.
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Title
4-pregnene-3-one-20 beta-carboxaldehyde: a potent inhibitor of 17
alpha-hydroxylase/C17,20-lyase and of 5 alpha-reductase.
Author
Li J, Li Y, Son C, Banks P, Brodie A
Address
Department of Pharmacology and Experimental Therapeutics, School of Medicine, University
of Maryland, Baltimore 21201.
Source
J Steroid Biochem Mol Biol, 42: 3-4, 1992 May, 313-20
Abstract
The pregnene derivative, 4-pregnene-3-one-20 beta-carboxaldehyde (22-A) was evaluated as
an inhibitor of 17 alpha-hydroxylase/C17,20-lyase in rat testicular microsomes and of 5
alpha-reductase in human prostatic homogenates. The effect of the compound in vivo was
studied in adult male rats. The 22-A demonstrated potent and competitive inhibition of 17
alpha-hydroxylase and C17,20-lyase with Ki values 8.48 and 0.41 microM, respectively,
significantly below the Km values for these two enzymes (33.75 and 4.55 microM). This
compound also showed potent inhibition of 5 alpha-reductase with a Ki value of 15.6 nM (Km
for this enzyme is 50 nM). By comparison, ketoconazole, a currently studied 17
alpha-hydroxylase/C17,20-lyase inhibitor for the treatment of prostatic cancer, showed
less potent inhibition of 17 alpha-hydroxylase (Ki 39.5 microM) and C17,20-lyase (Ki 3.6
microM) and did not inhibit 5 alpha-reductase. Progesterone which has been reported to
inhibit the 17 alpha-hydroxylase/C17,20-lyase, did not significantly reduce the production
of testosterone by rat testes in vitro in comparison to controls, while the same
concentration of 22-A demonstrated a 42% reduction of testosterone biosynthesis. When the
adult male rats were injected s.c. with 22-A at 50 mg/day/kg for a 2 week period, the
testosterone concentrations in the rat sera were significantly lower than control values
(P less than 0.05), whereas serum corticosterone levels did not change. These results
suggest that 22-A is a selective potent inhibitor for 17 alpha-hydroxylase and
C17,20-lyase, but is more potent for the C17,20-lyase. The compound also inhibits 5
alpha-reductase, and therefore may reduce biosynthesis of testosterone and
dihydrotestosterone effectively. Thus, 22-A may be useful in the treatment of problems
associated with the androgen excess and prostatic cancer.
Language of Publication
English
Unique Identifier
92297464
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