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BOR - Papers in Press, published online ahead of print March 3, 2004.
Biol Reprod 2004, 10.1095/biolreprod.103.026245
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BIOLOGY OF REPRODUCTION 71, 97–103 (2004)
DOI: 10.1095/biolreprod.103.026245
© 2004 by the Society for the Study of Reproduction, Inc.

Mechanisms of Hormone Action

Changes in CD38 Expression and ADP-Ribosyl Cyclase Activity in Rat Myometrium During Pregnancy: Influence of Sex Steroid Hormones1

Soner Dogan3, Deepak A. Deshpande3, Mathur S. Kannan3, and Timothy F. Walseth2,4

Department of Veterinary Pathobiology,3 College of Veterinary Medicine Department of Pharmacology,4 College of Medicine, University of Minnesota, St. Paul, Minnesota 55108

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 (preterm) and at parturition (term). CD38 expression, ADP-ribosyl cyclase activity, and cADPR levels were higher in uterine tissues obtained from term rats compared with that of preterm 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.

1 Supported by grants from the National Institutes of Health (HL057498 to M.S.K. and DA11806 to T.F.W.), Academic Health Center Faculty Development Grant, University of Minnesota, and a Fellowship from the Turkish Educational Ministry (to S.D.).

2 Correspondence: Timothy F. Walseth, Department of Pharmacology, Medical School, University of Minnesota, 312 Church St. SE, Minneapolis, MN 55455. FAX: 612 625 5203; walseth{at}mail.ahc.umn.edu




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