In vitro stimulation by estrogen of guanosine 3',5'-monophosphate accumulation in incubated rat uterus.

Abstract

Uterine horns from immature rats were incubated for 2 h with 17β-estradiol (1–4 × 10−8m). This resulted in a significant increase in the cGMP content of the organ (mean increase over control, 179%). A similar effect was obtained using diethylstilbestrol or estriol. Progesterone (10−7m) given under similar conditions decreased uterine cGMP content, while testosterone (10−8m) had no significant effect on this parameter. Testosterone [10−7m; a concentration reported to promote nuclear translocation of the estrogen receptor (26–29)] increased uterine cGMP content to 140% of the control value. Like the increase in uterine cGMP content we observed previously in animals treated in vivo with estradiol, the in vitro response is suppressed in organs from rats that were treated for 20–22 h with the antiestrogen nafoxidine or tamoxifene, a treatment which results in a marked depletion in estrogen receptor. Full responsiveness is restored 20–22 h (but not 2 h) after an estradiol injection, i.e. at a time which in this case corresponds to full replenishment of the estrogen receptor. No significant difference was observed between the effect of suboptimal doses of 17β- and 17α-estradiol (10−10 to 4 × 10−10m) on uterine cGMP, but the effect of 17α-estradiol was also suppressed by treatments that deplenish the estrogen cytosol receptor population. These results suggest that the in vitro effect of estradiol mimics the in vivo effect and that both may represent a true hormonal action involving the estrogen receptor system. (Endocrinology 106: 1187, 1980)