Dogan Soner, Deshpande Deepak A, Kannan Mathur S, Walseth Timothy F
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of MInnesota, St. Paul, MN 55108, USA.
Biol Reprod. 2004 Jul;71(1):97-103. doi: 10.1095/biolreprod.103.026245. Epub 2004 Mar 3.
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.
由CD38合成的环磷酸腺苷核糖（cADPR）可调节子宫平滑肌细胞内的钙。CD38是一种跨膜蛋白，具有参与cADPR代谢的ADP核糖基环化酶和cADPR水解酶活性。子宫平滑肌中CD38的表达及其酶活性受雌激素调节。在本研究中，我们检测了妊娠14 - 17天（早产）和分娩时（足月）大鼠子宫肌层中CD38的表达、其酶活性以及cADPR水平。与早产大鼠相比，足月大鼠子宫组织中CD38的表达、ADP核糖基环化酶活性和cADPR水平更高，而cADPR水解酶的活性没有显著变化。为了探讨孕期雌激素与孕酮比例的变化是否是导致观察到的对CD38表达和功能影响的原因，我们测定了在雌激素存在下不同剂量孕酮对去卵巢大鼠子宫平滑肌中CD38表达及其酶活性的影响。在去卵巢大鼠的子宫肌层中，给予雌激素会导致CD38蛋白表达和ADP核糖基环化酶活性增加。同时给予10或20 mg孕酮可抑制雌激素诱导的CD38表达和ADP核糖基环化酶活性增加。这些结果表明，雌激素与孕酮的比例决定了CD38的表达和ADP核糖基环化酶活性。CD38/cADPR途径的这些变化可能有助于子宫运动性增加和分娩发动。
