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Abstract
Cyclic ADP-ribose (cADPR), synthesized by CD38, regulates
intracellular calcium in uterine smooth muscle. CD38 is a
transmembrane protein that has both ADP-ribosyl cyclase
and cADPR hydrolase enzyme activities involved in cADPR
metabolism. CD38 expression and its enzyme activities in
uterine smooth muscle are regulated by estrogen. In the
present study, we examined CD38 expression, its enzyme
activities and cADPR levels in myometrium obtained from
rats at 14-17 days of gestation (pre-term) and at
parturition (term). CD38 expression, ADP-ribosyl cyclase
activity and cADPR levels were higher in uterine tissues
obtained from term rats compared to that of pre-term rats
while activity of cADPR hydrolase did not significantly
change. In an effort to address whether changes in
estrogen/progesterone ratio that occur during pregnancy
account for the observed effects on CD38 expression and
function, we determined the effect of different doses of
progesterone in the presence of estrogen on CD38
expression and its enzyme activities in uterine smooth
muscle obtained from ovariectomized rats. In myometrium
obtained from ovariectomized rats, estrogen administration
caused increased CD38 protein expression and ADP-ribosyl
cyclase activity. The estrogen-induced increases in CD38
expression and ADP-ribosyl cyclase activity were inhibited
by simultaneous administration of 10 or 20 mg of
progesterone. These results indicate that the
estrogen/progesterone ratio determines CD38 expression and
ADP-ribosyl cyclase activity. These changes in CD38/cADPR
pathway may contribute to increased uterine motility and
onset of labor.
Key words:
Pregnancy •
Estradiol •
Progesterone •
Steroid hormones •
Uterus
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