Effects of Estradiol-17βand Progesterone on Cyclic Nucleotide Metabolism in Myometrium of Macaques

We determined the activities of the adenylate (homogenate) and guanylate cyclases (100,000 × g supernatant) and the cyclic nucleotide phosphodiesterases (PDEs) (100,000 × g supernatant and particulate) of myometria from: 1) rhesus monkeys spayed for at least 6 months and treated either with estradiol-17β(E2) for 14 days or with E2for 14 days and then treated for 5–14 additional days with E2plus progesterone (P); and 2) cynomolgus monkeys during the follicular and luteal phases of natural menstrual cycles. Plasma levels of E2and P were similar in the spayed rhesus monkeys treated with hormones and the naturally cycling cynomolgus monkeys. The specific activities of the guanylate cyclase and the cAMP- and cGMP-PDE enzymes/mg nitrogen or DNA were decreased in myometria from monkeys in the luteal compared with the follicular phase of both natural and induced menstrual cycles; no difference was observed in adenylate cyclase activity. There was also no difference in the concentrations of nitrogen and of DNA in the follicular and luteal phase myometrium. The average cAMP/cGMP ratio was more than twice as high in the follicular compared with the luteal phase (8.5 vs 3.7). This decrease in the cyclic nucleotide ratio was due mainly to an increase in cGMP levels and suggests that in vivo the activity of the guanylate cyclase enzyme decreased less than did the activity of the cGMP-PDE. These data strongly suggest that it is P that causes the decrease in the activities of the guanylate cyclase and cyclic nucleotide PDE, because enzyme activity is significantly higher in the myometrium during the follicular phases of both the induced and natural menstrual cycles. It appears that cyclic nucleotide metabolism in nonhuman primate myometrium varies during the menstrual cycle.