MECHANISM OF OESTRADIOL ACTION ON THE RAT UTERUS: INDEPENDENCE OF CYCLIC AMP, PROSTAGLANDIN E2 AND Β-Adrenergic MEDIATION

Abstract

The hypothesis that cyclic AMP plays an essential role in mediating the biological action of oestradiol on the uterus, was tested by determining the tissue concentration of the cyclic nucleotide after incubation of uteri of immature rats with oestradiol or after injection of this steroid into immature or ovariectomized rats. The effect of known stimulants of uterine adenyl cyclase, namely \g=b\-adrenergicdrugs and prostaglandin E2 (PGE2), on the level of cyclic AMP in the uterus was also examined both in vitro and in vivo.In either system, oestradiol failed to enhance the concentration of cyclic AMP in the uterine tissue, whereas adrenaline or the almost purely \ g = b \ \ x = r e q -\ adrenergic agonist isoprenaline (isoproterenol) caused cyclic AMP accumulation that was susceptible to inhibition by the \g=b\-adrenergicblocking agent propranolol. Prostaglandin E2, and to a much lesser degree prostaglandin F2\ g=a\ , increased cyclic AMP concentration in the uterus, but the effect of PGE2 was not inhibited by propranolol. It may be concluded that oestradiol does not cause appreciable stimulation of PGE2 synthesis or activation of \g=b\-adrenergicreceptors in the rat uterus since, otherwise, increased cyclic AMP production should have been observed after the treatment with oestradiol.Isoprenaline mimicked the stimulatory action of oestradiol on uterine ornithine decarboxylase. However, this action of isoprenaline was abolished by propranolol, whereas that of oestradiol was only slightly, though significantly, inhibited.The present findings do not support the view that the action of oestradiol on the uterus is mediated by cyclic AMP, and also suggest that \g=b\-adrenergic receptors and PGE2 can have only a minor role, if any, in the mechanism of action of this hormone. * In partial fulfilment of the requirements for the Ph.D. decree of the Graduate School of the Weizmann

The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis are directly regulated by estrogen receptor

“…Notably, not all the physiological and biochemical changes associated with estrogen treatment are necessary for the uterotrophic effect. For example, while cAMP is elevated after estrogen administration (Szego & Davis 1967), uterine growth is independent of cAMP (Zor et al 1973). This is also true for ornithine decarboxylation and prostaglandins.…”

Involvement of hypophysis in the stimulation of liver ornithine decarboxylase by dibutyryl cyclic AMP

“…A role for a cyclic AMPdependent protein kinase in the regulation of orinthine decarboxylase activity has also been suggested by Byus and Russell [13]. However, estradiol given in vivo has been shown to increase ornithine decarboxylase activity in the rat uterus without changing the concentration of cyclic AMP [ 14]. Furthermore, the addition of serum or insulin to cell cultures is able to stimulate ornithine decarboxylase, but it decreases the level of cyclic AMP [ 12].…”

A Study on the Estradiol-Induced Augmentation of a Specific Cell Product in the Vaginal Epithelium of the Neonatal Mouse

“…An increase in cytochemically demonstrable adenylate cyclase activity occurs in the cervicovaginal epithelium of mice in-iected with estradiol neonatally (1 5, 25). Although some controverse exists, it seems that elevation of cyclic AMP or stimulation of adenylate cyclase is not essential for the estradiol action in adult rodents (2, 13,18,23). In contrast to the usual proliferative effect of estradiol in the genital epithelium, this hormone inhibits the mitotic rate in the untransformed pseudostratified columnar epithelium in the cervicovaginal anlage of neonatal mice (6).…”