This review article discusses a novel nontraditional site of estrogen
synthesis and the potential targets of estrogen action within the male
reproductive system. Our laboratories have recently demonstrated that
developing spermatids in several species contain aromatase, the cytoc
hrome P450 enzyme responsible for converting androgens into estrogens.
The enzyme was localized by immunocytochemistry and the protein's pre
sence was confirmed by Western blot analysis. Northern blot analysis a
nd in situ hybridization were used to corroborate the presence of mRNA
for aromatase. It appears that the aromatase message precedes the syn
thesis of the protein, and the protein remains in the spermatids sever
al days after the message disappears. The enzyme is located along the
tail of newly released sperm and is active in the epididymal sperm as
well as in the developing germ cells of the testis. This unique discov
ery is the basis for our overall hypothesis that estrogen, synthesized
by sperm, plays a role in the regulation of epididymal function propo
rtional to the number of sperm being transported. The presence of an e
strogen source within the ductal lumen is of special importance to the
study of epididymal function because the regulatory mechanisms in thi
s region remain unclear, particularly for the efferent ductules and in
itial segment regions, although estrogen receptors have been identifie
d in the ductal epithelium. An understanding of the role that estrogen
plays in the function of the epididymis may provide benefits in sever
al areas including the treatment of abnormalities in epididymal functi
on, the potential development of a male contraceptive, and insight int
o the causes of adult epididymal lesions induced by neonatal exposure
to estrogenic compounds such as diethyistilbestrol.