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Regulation of Calcitonin Gene-Related Peptide Receptors in the Rat Uterus During Pregnancy and Labor and by Progesterone¹

^a Departments of Obstetrics and Gynecology and ^b Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77555

Calcitonin gene-related peptide (CGRP) is a potent smooth muscle relaxant in a variety of tissues. We recently demonstrated that CGRP relaxes uterine tissue during pregnancy but not during labor. In the present study we examined whether uterine ¹²⁵I-CGRP binding and immunoreactive CGRP receptors are regulated by pregnancy and labor and by sex steroid hormones. We found that ¹²⁵I-CGRP binding to membrane preparations from uteri was elevated during pregnancy and decreased during labor and postpartum. Changes in immunoreactive CGRP receptors were similar to the changes in ¹²⁵I-CGRP binding in these tissues, suggesting pregnancy-dependent regulation of CGRP receptor protein. CGRP receptors were elevated by Day 7 of gestation, and a precipitous decrease in these receptors occurred on Day 22 of gestation prior to the onset of labor. Both ¹²⁵I-CGRP-binding and immunofluorescence studies indicated that CGRP receptors were localized to myometrial cells.

Hormonal control of uterine CGRP receptors was assessed by the use of antiprogesterone RU-486, progesterone, and estradiol-17ß. RU-486 induced a decrease in uterine CGRP receptors during pregnancy (Day 19). On the other hand, progesterone prevented the fall in uterine CGRP receptors at term (Day 22). In addition, progesterone also increased uterine CGRP receptors in nonpregnant, ovariectomized rats, while estradiol had no effects. These hormone-induced changes in uterine CGRP receptors were demonstrated by ¹²⁵I-CGRP-binding, Western immunoblotting, and immunolocalization methods.

These results indicate that CGRP receptors and CGRP binding in the rat uterus are increased with pregnancy and decreased at term. These receptors are localized to the myometrial cells, and progesterone is required for maintaining CGRP receptors in the rat uterus. Thus, the inhibitory effects of CGRP on uterine contractility are mediated through the changes in CGRP receptors and may play a role in uterine quiescence during pregnancy.

¹ Financial support was provided by NIH through grants HD 30273 and HL 58144.

² Correspondence: Chandra Yallampalli, University of Texas Medical Branch, 301 University Boulevard, Route 1062, Galveston, TX 77555–1062. FAX: 409 747 0475; chyallam{at}utmb.edu

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