Effect of an Intra-Uterine Device on Intracellular Relationships of the Uterine Oestrogen Receptor, Particularly During Pregnancy

Abstract

The presence of an intra-uterine device in the rat results in a lower nuclear concentration of the oestrogen receptor in the treated horn at pro-oestrus when it is compared with the contralateral control horn. This effect was also seen after the administration of hyperphysiological doses of oestradiol and when the horn was exposed in vitro to high concentrations of oestradiol. The cyclic changes during the oestrous cycle in the activity of the oestrogen-induced enzyme peroxidase were similar in the treated and control horns. These observations have discounted the possibility that the relatively lower nuclear receptor content in the treated horn at pro-oestrus was due to a decreased exposure to oestrogen. A significantly lower nuclear content was also observed in the treated horn on days 4 and 5 of pregnancy. This was not associated with a deficiency in cytosol receptor content which increased concurrently with that of the control horn in the 6 days of pregnancy that were studied. The proportional content of the putative cytosol factor implicated in receptor translocation was similar in both horns, increasing on days 4 and 6 in concert with reported changes in 'induced protein' synthesis. There appeared to be reduced levels of nuclear receptor at a time when blastocyst implantation normally occurs.

Progesterone therapy results in partial reversibility of uterine abnormalities of the adult anovulatory rat

“…In contrast, progesterone therapy had a different effect on the testosterone-treated group; cytosol oestrogen receptor remained unaltered despite a decrease in nuclear oestrogen receptor content. Changes in nuclear but not cytosol uterine oestrogen receptor content are also observed during the oestrous cycle and in early pregnancy (White et a!., 1978;Myatt et al, 1978Myatt et al, , 1980a. There is evidence that factors other than cytosol receptor content may determine the extent of hormone action; these include nuclear acceptor sites (Buller & O'Malley, 1976) and substances that either increase (Thrower et a!., 1976) or inhibit activation (Sato et al, 1978;Shen et al, 1979) of the oestrogen receptor obligatory for nuclear binding.…”

“…Progesterone antagonism of oestrogen stimulation may in part be mediated via the modulation of the concentration of such factors. Progestin receptor synthesis in the rodent uterus is itself regulated by oestrogen (Feil et al, 1972) and changes in nuclear oestrogen receptor levels correlate with changes in progestin receptor synthesis (Thrower & Lim, 1980;Myatt et al, 1980b). Despite the occurrence of substantial concentrations of nuclear oestrogen receptors the content of progestin receptor in the neonatally treated anovulatory rats was found to be lower than in normal animals (White et al, 1981) suggesting a defect in the regulation of progestin receptor synthesis.…”