Life Sci 1988;43(23):1845-50
Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine
prostate.
Meikle AW, Liu XH, Taylor GN, Stringham JD
Department of Internal Medicine, University of Utah, Salt Lake City 84132.
We have recently observed that cigarette smoking affects plasma androgen concentrations.
The effects of nicotine and cotinine, two products of cigarette smoking, on testosterone
metabolism were determined. The activity of delta 4 steroid 5 alpha-reductase, which
converts testosterone to 5 alpha-dihydrotestosterone (DHT) was measured in isolated dog
prostate nuclei using testosterone (0-200 nM) as substrate and NADPH as cofactor. Activity
of 3 alpha-hydroxysteroid dehydrogenase (HSD), which converts DHT to 3
alpha-androstanediol (3 alpha-diol) and is a reversible enzyme, was measured in isolated
dog prostate microsomes with DHT (0-20 microM) as substrate and NADPH as cofactor. When
microsomal fractions were incubated for 1 hour with and without nicotine (0-50 microM) and
cotinine (0-100 microM), enzyme activity of HSD was significantly suppressed (p less than
0.001). The Vmax was not affected significantly (p greater than 0.60) and Km increased
with increasing concentrations of nicotine and cotinine (p less than 0.05). Both nicotine
and cotinine are competitive inhibitors of HSD in dog prostate microsomes with Ki's of 61
and 89 microM, respectively. The apparent 5 alpha-reductase activity was unaffected by
nicotine and cotinine. The inhibitors produced a marked effect on activity of HSD when
used in concentrations achieved in humans who smoke cigarettes. The results suggest that
nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved
in the metabolism of DHT and produce an accumulation of DHT. These products of cigarette
smoking could alter androgen action in tissue such as skin and prostate.
PMID: 3200111, UI: 89070142