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Departments of Medicine and Neurobiology and Physiology and The Center for Reproductive Sciences, Northwestern University, Chicago, Illinois 60611
Address all correspondence and requests for reprints to: Teresa K. Woodruff, Tarry Building 15716, 303 Chicago Avenue, Chicago, Illinois 60611.
Activin A is a dimeric protein hormone that regulates numerous cellular functions. A clear physiological role for this molecule in pregnancy is suggested by previous studies in the human, wherein activin A rises dramatically as women approach parturition. To determine whether the rodent is a suitable animal model for further studies of activin action during pregnancy, the serum concentration of activin A was measured in pregnant rats. Activin A was detected in the serum of pregnant rats, beginning on day 12, and the serum concentration rose progressively through gestation (22-fold) and dramatically (140-fold) in labor. The potential target tissues for circulating activin were then identified in two ways. First, iodinated activin was injected into pregnant rats, and the tissues targeted by labeled ligand were identified in vivo. A tissue targeted by activin A in the pregnant rat was the uterine myometrium. To determine the ligand specificity of the uterine myometrial cells, the uteri of pregnant rats were collected and analyzed by in situ ligand binding. 125I-activin A binding was specific for the uterus myometrium, and the ligand binding was competed by unlabeled activin A but not by inhibin A. This result suggests that the receptor in this tissue compartment is an activin-specific receptor. The production of abundant activin A and the ability of exogenous ligand to target the myometrium of the uterus provides a pathway by which activin could regulate uterine function during pregnancy.
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