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 he chemical HPTE, a metabolite of the common pesticide
methoxychlor, reduces testosterone production and could be a
contributory factor in male infertility, Population Council scientists
report in the March 2000 issue of Biology of Reproduction.
Methoxychlor a pesticide in the DDT family gained popularity
after DDT was banned in the United States in 1972.
 Matt
Hardy and Benson Akingbemi have been investigating endocrine
disrupters and their effects on the reproductive system. They
examined the effect of HPTE on testosterone production in developing
(progenitor and immature) and adult Leydig cells. The researchers
found that the more HPTE that Leydig cells were exposed to, the
less testosterone the cells produced. HPTE inhibited testosterone
production in developing Leydig cells after ten hours of treatment,
and in adult Leydig cells after 18 hours. Inhibition of Leydig
cells was due to the down regulation of one of four enzymes that
catalyze the reactions that occur during androgen biosynthesis.
To determine
the reversibility of HPTE-induced testosterone inhibition, the
researchers waited 18 hours in each case to see whether testosterone
production in these cells recovered to the levels observed in
control cells. When treated for three hours, testosterone production
by immature and adult Leydig cells rebounded within the 18-hour
recovery period, but remained significantly inhibited within
progenitor Leydig cells. When treatment lasted six or more hours,
however, immature and adult Leydig cells also failed to fully
resume testosterone production within the 18-hour recovery period.
The onset of HPTE action and the reversibility of its effect
showed that Leydig cells are more sensitive to this compound
during pubertal differentiation than in adulthood.
Hardy, a reproductive
biologist at the Population Council's Center for Biomedical Research,
comments that "While HPTE and similar agents are of concern
for environmental reasons, studying them may also help us identify
new molecular targets for male contraceptives." The Center
is one of the world's leading laboratories for contraceptive
development and for investigation of the male reproductive system.
Hardy and colleagues plan to study the effects of other endocrine
disrupters on Leydig cells.
To view an
abstract of the research article go to: intl.biolreprod.org/cgi/content/abstract/62/3/571.
To view a report about the research go to: www.popcouncil.org/publications/popbriefs/pb5(4)_3.html.
To view a summary of the research undertaken in the laboratory
of Matthew Hardy go to: www.popcouncil.org/biomed/mhardy.html.
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