Relationship between cytosol and nuclear oestrogen receptors and oestrogen concentrations in the fetal compartment of guinea-pig

Abstract

Previous reports from our laboratory as well as the results of the present study show that specific [ 3H]oestradiol binding is present in various organs of the fetal guinea-pig. At the same fetal age ( ~ 50 days of gestation), the concentration of specific [ 3H]oestradiol binding sites per mg DNA in the various fetal tissues can be classed as follows: uterus > lung > brain ⩾ kidney. The [ 3H]oestradiol binding sites in all the tissues studied are capable of binding other oestrogens such as oestrone or oestriol but aldosterone, testosterone, cortisol and progesterone do not compete for [ 3H]oestradioI binding sites. In uterus [ 3H]oestradiol and [ 3H]oestrone were found to bind in equal quantities to the same binding site. Binding of [ 3H]oestradiol is of high affinity in all four tissues ( K D4 C = 2 −8 × 10 −10 M). The sedimentation coefficient of this [ 3H]oestradiol binding component in all four tissues is 8 S in low salt sucrose density gradients and the isoelectric point (pI) as determined by isoelectrofocusing on gel plates is 6–6.2. The concentration of oestradiol and oestrone in fetal plasma and in the tissues were determined by radioimmunoassay. The values in fetal plasma from 50 to 64 days of gestation for oestradiol are 9–11 pg/ml plasma and for oestrone, 94–105 pg/ml plasma. In the uterus, the concentration of both oestrogens is higher than in plasma, in the order of 1–2 ng per g of tissue. These relatively low levels of circulating oestrogen concentration correlate well with the finding that 93.3% of the [ 3H]oestradiol binding sites are in the cytosol fraction. Moreover, the concentration of occupied binding sites in the uterus (9 pmol/g tissue) corresponds well with the concentration of oestrogens in the tissue (7 pmol/g tissue). A possible biological role of oestradiol receptors in fetal uterus has been revealed. Administration of oestradiol to the pregnant guinea-pig has been found to increase very significantly the concentration of specific progesterone binding sites in the fetal uterus.