Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

The precise factors involved in the transition of the relaxed pregnant uter us to the contractile state at the onset of parturition remain unclear, but it is accepted that cAMP-generating pathways contribute to uterine relaxat ion. We have previously reported an increased expression of the adenylyl cy clase (AC)-stimulating protein G alpha s in human myometrium during gestati on, with a corresponding increase in GTP-stimulatcd AC activity. However, l ittle is known about the predominating AC isoforms expressed during pregnan cy. This information is important, because although all AC isoforms are sti mulated by G alpha s, their regulation by other signalling molecules is ver y different. In the present study we have identified the isoforms of AC ex- pressed in both pregnant and non-pregnant myometrium by mRNA analysis and i mmunoblotting. mRNA encoding for AC I, II, III, VIII and IX was present in non-pregnant and pregnant myometrium, and in cultured myometrial cells. Dif fering levels of AC protein could be detected in myometrial plasma membrane s, with decreased levels of Group 1 (isoforms I, III and VIII) and Group 4 (IX) ACs allied with increased levels of Group 2 (II, IV and VII) and 3 (V and VI) ACs during pregnancy. These findings imply a role for Group 2-activ ating pathways, e.g. G-protein beta gamma-subunits and protein kinase C, in the maintenance of uterine quiescence, whilst suggesting a lesser involvem ent of calcium-calmodulin complex, an activator of Group 1 AC isoforms, in uterine relaxation during gestation. These data may provide an alternative pharmacological approach for the attenuation of preterm labour.