SUMMARY AND CONCLUSIONAdrenomedullin (ADM), consisting of 52 amino acids, is a recent multifunctional regulatory peptide discovered by Kitamura et al. (1993). ADM is synthesized by the adrenal medulla, ventricle, kidney, central nervous system, endothelial and vascular smooth muscle cells.Furthermore, in human and rat uterus, ADM is mainly located in the endometrium suggesting that ADM may act on the myometrium in a paracrine manner. Both ADM and its receptors are expressed in the uterus and their expression markedly increased during pregnancy. The physiological meaning of increased adrenomedullin production observed in pregnancy is still to be established. Hence, it was decided to examine the modulative capability of ADM on the contractile response of pregnant rat uterus.Therefore, this work was carried out on 32 healthy adult albino rats (30 female rats and 2 male rats for induction of pregnancy). Adult female rats were subdivided into three equal groups (each 10 rats).Group I : non-pregnant rats.Group  : early pregnant rats at day 4.Group  : late pregnant rats at day 19.The first day of pregnancy was determined by examination of vaginal smear of females the next morning after mating with a male. The presence of sperms indicated the first day of gestation.Moreover, the contractile response of uterine strips isolated form non pregnant, early and late pregnant rat uterus was studied in vitro in presence and absence of ADM by a variety of uterotonic agents as follow:* Group I: consisting of 10 rats; from each non pregnant rat uterus, four isolated muscle strips were taken. Each strip was used only in one experiment, so the first group was subdivided into four subgroups as follow:Subgroup 1: to study the effect of ADM and ADM22-52 (ADM receptor antagonist) on spontaneous myometrial contraction.Subgroup 2: to study the effect of ADM on periodic myometrial contraction induced by bradykinin (BK) and the effect of ADM and ADM22-52 (ADM receptor antagonist) on periodic myometrial contraction induced by bradykinin (BK).Subgroup 3: to study the effect of ADM on periodic myometrial contraction induced by oxytocin (OT).Subgroup 4: to study the effect of ADM on periodic myometrial contraction induced by prostaglandin F (PG F2 ).* Group II, III: the same was done as in Group I.Furthermore, the rats were sacrificed and blood was collected then the serum was separated. The levels of estrogen, and progesterone were estimated in all studied groups to determine the effect of steroid hormones on uterine responsiveness to ADM.The results of the present study revealed that:** ADM significantly inhibited spontaneous and bradykinin (BK)- induced periodic myometrial contractility. However, ADM had no effect on oxytocin (OT)- and PGF2- induced periodic myometrial contractility in non-pregnant group, early pregnant (day 4) group and late pregnant (day 19) group.** ADM receptor antagonist (ADM 22-52) was found to block the effect of ADM on frequency, amplitude and basal tone of spontaneous myometrial contractility in non pregnant group, early pregnant (day 4) group and late pregnant (day 19) group. Therefore, this study proved that specific ADM receptors were found to be present in the uterus mediating the inhibitory effect of ADM.** This study proved that the relaxant effect of ADM upon pregnant uterine smooth muscles was mainly via ADM receptors.** Serum progesterone level was significantly increased throughout pregnancy suggesting that progesterone increased the levels of ADM receptors, indicating regulation by steroid hormones. The progesterone-stimulated increases in ADM receptors may be responsible for increased uterine relaxation sensitivity to ADM during pregnancy. Also, estrogen levels were increased progressively during gestation.Therefore, it was recommended that:** ADM plays an important role in uterine smooth muscle relaxation (uterine quiescence) that required for successful pregnancy and hence, the prevention of preterm labor and threatened abortion.