Estradiol-17  and Progesterone: Effects on Guanylate Cyclase Activity in the Myometrium of Macaques

Guanylate cyclase activity was determined in various subcellular fractions of myometrium (1) from rhesus monkeys spayed for at least 6 months and treated either with estradiol-17β (E2) for 14 days or with E2 for 14 days and then for 5 to 14 additional days with E2 plus progesterone (P) and (2) from cynomolgus monkeys during the follicular and luteal phases of natural menstrual cycles. Plasma levels of E2 and P were similar in the spayed rhesus monkeys treated with hormones and the naturally cycling cynomolgus monkeys. In the 100,000g supernatant and particulate fractions of macaque myometrium before and after treatment with Triton X-100, the specific activities (per milligram nitrogen or DNA) of the guanylate cyclase were less in the luteal than in the follicular phases of both natural and induced menstrual cycles. The hormonal effects appear specific for myometrial smooth muscle since there was no difference in the guanylate cyclase activity of intestinal smooth muscle (taenia coli) in the follicular and luteal phases. The effect of varying concentrations of Mn2+ on myometrium at different phases of an induced menstrual cycle was studied after homogenization with 1 mM EDTA. Guanylate cyclase activity in the 100,000g supernatant and particulate were higher in the “follicular” than in the “luteal” phase at all levels of Mn2+ studied. At the lower levels of Mn2+ the addition of 3 mM Ca2+ increased guanylate cyclase activity in the 100,000g supernatant fraction and decreased this activity in the 100,000g particulate fraction. The Ca2+-induced increment in guanylate cyclase activity was greater in “luteal” than “follicular” myometrium, whereas the Ca2+-induced decrement in the activity of the particulate fraction was greater in “follicular” than in “luteal” myometrium. It appears that cyclic nucleotide metabolism in nonhuman primate myometrium varies significantly during the menstrual cycle.