Activity and expression of soluble and particulate guanylate cyclases in myometrium from nonpregnant and pregnant women: down-regulation of soluble guanylate cyclase at term.

Abstract

The role of cGMP in the regulation of human myometrial smooth muscle contractility is at present unclear. cGMP can be synthesized by a cytoplasmic, soluble guanylate cyclase (sGC), which is stimulated by nitric oxide and carbon monoxide, and by particulate membrane-bound GC, which are activated by natriuretic peptides. The aim of this study was to determine whether sGC or pGC are present in nonpregnant and pregnant human myometrium, and whether the activity and expression of these enzymes and the cGMP content change during pregnancy and with labor. Myometrium was obtained from nonpregnant women (n = 12) and pregnant women who were preterm (25-34 wk gestation; n = 12), term (>38 wk) not in labor (n = 14), or term in active labor (n = 12). The cGMP content in myometrium obtained from preterm deliveries was significantly higher than that in tissue obtained from nonpregnant women and decreased at term, especially in laboring groups. Protein and mRNA for sGC, particulate GC-A, GC-B, and the clearance receptor were detected in human myometrium. cGMP in pregnant human myometrium, however, appears to be produced predominantly by sGC and possibly by GC-B, as GC-A was only weakly expressed. sGC activity was greater in myometrium from preterm (nonlabor) deliveries compared those taken at term (in labor), but was down-regulated compared with activity in nonpregnant myometrium. Neither atrial natriuretic peptide nor C-type natriuretic peptide (agonists for GC-A and GC-B, respectively) altered contractility in vitro of myometrium from women at term (not in labor). We conclude that the cGMP/guanylate cyclase system in human myometrium is gestationally regulated and potentially plays an important role in mediating quiescence during early pregnancy. A reduction in cGMP availability may contribute to the switch to contractile activity at term.