title: Uptake, receptor and biological response of estrone in the fetal uterus of guinea pig.
abstract: In vivo and in situ subcutaneous injection of 30 muCi of 3H-estrone (3H-E1) to guinea pig fetuses was carried out to study the dynamics of the selective uptake and retention of this estrogen in the uterus and other fetal organs. In the fetal uterus an increase in the uptake of radioactivity with time was found which was maximal 1 h after injection of 3H-E1. The analysis of radioactive material showed that in the fetal uterus unmetabolized 3H-E1 accounts for 65-75% of the total radioactivity between 10 and 60 min after the injection and its maximal concentration is 2.5-15 times and 10 times higher than the maximal concentrations found in other fetal organs and fetal plasma, respectively. Significant amounts of 3H-E1 were also present in lung (33-60% of the total radioactivity in this tissue), brain (37-52%) and ovary (18-47%), while an important conversion of 3H-E1 into 3H-estradiol was observed in the kidney (20-26%). Estrogen sulfates, essentially estrone sulfate, represented the greater part of the fetal plasma radioactivity (30-49%). 3H-E1-specific binding sites in the cytosol of the fetal uterus were found with physicochemical characteristics (specifically limited to natural and synthetic estrogens, Kd = 8.1 +/- 1.2 x 10(-10) M (SD), sedimentation coefficient 8S) similar to those of the typical estrogen receptor. The cytosol receptor-3H-E1 complex has a dissociation rate constant (K-1) of 16 +/- 0.7 x 10(-4) s-1 at 25 degrees C. The responsiveness of the fetal uterus to estrone treatment was studied after subcutaneous administration of estrone to pregnant guinea pigs (1 mg/kg/day for 3 consecutive days). Two biological responses were observed: an increase in fetal uterine weight (50-100% in relation to the nontreated animals) and a significant stimulation of progesterone receptor protein (10-16 times higher than in control animals). At the same time, there was a 50-70% decrease in the total estrogen receptor concentration. It is concluded that estrone could be involved in the biological responses to estrogen in the fetal uterus of guinea pig.
mesh_terms: D000818:Animals; D004970:Estrone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000187:drug effects; D014018:Tissue Distribution; D014599:Uterus / Q000196:embryology* / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C038074:estrone receptor; D004970:Estrone