Uterine quiescence: the role of cyclic AMP

It is accepted that whilst hormones such as oxytocin, vasopressin and prost aglandin F-2 alpha induce myometrial contractions, essentiallg,ia an elevat ion of intracellular calcium, other ligands, such as beta -adrenoceptor ago nists, calcitonin gene-related peptide, and prostaglandin E-2, promote uter ine quiescence via their ability to increase intracellular cyclic AMP level s. At present, the exact factors initiating human parturition remain unknow n, and labour may occur due to a loss of uterine quiescence, an increase in uterine contractility, or a combination of both. Whilst many studies have aimed to understand the mechanisms underlying uterine contractility there i s a relative paucity of data regarding myometrial relaxation. We have verif ied the presence of mRNA encoding adenylyl cyclase (AC) isoforms I, II, m, V, VI, VII, VIII and IS in both non-pregnant and pregnant human myometrium, and in isolated myometrial cells maintained in cell culture. Furthermore, by means of immunoblotting and immunocytochemistry, we have demonstrated th e expression of these isoforms as membrane-associated AC proteins, and iden tified changes in individual AC isoform expression during gestation. These findings illustrate the diversity of potential cAMP generating pathways in human myometrium, and the complexity of the signal transduction systems und erlying uterine quiescence.