Characteristics of estradiol-binding macromolecules in fetal and adult guinea pig brain cytosols.

Abstract

Estradiol-binding characteristics of brain and plasma were studied in fetal guinea pigs and of brain, pituitary and plasma in adult female guinea pigs. Results offl Vitro binding experiments with H-estradiol indicate that cytosol prepared from the adult brain contains at least two popula- tions of estradiol-binding macromolecules. One is concentrated within cytosol from pooled hypo- thalamus-preoptic area-amygdala (HPA) and seems to resemble the soluble estradiol receptor found in corresponding regions of the rat brain, in terms of its affinity for estradiol, ability to bind RU2858 (a synthetic steroidal estrogen) and behavior on sucrose density gradients. The second population of estradiol-binding macromolecules was observed in cerebral cortex (CTX) as well as HPA cytosols, and can be distinguished from the first by its lower affinity for estradiol and its apparent lack of affinity for RU2858. Pituitary cytosol seems to contain only the higher affinity estradiol-binding molecules. Intravenously injected H-estradiol was concentrated in nuclear frac- tions of HPA and pituitary but not to an appreciable extent in CTX nuclear fractions, indicating that the lower affinity soluble binding material is not transferred to the cell nucleus in vivo. In vitro estradiol-binding properties of fetal guinea pig brain cytosol are qualitatively similar to those of adult brain cytosol, but the concentration of the lower affinity binding sites seems to be higher in the fetus. Both adult and fetal plasmas contain macromolecules that bind H-estradiol in vitro, forming complexes that migrate to the .�4S region of sucrose density gradients. These plasma bind- ing sites, unlike those of brain and pituitary cytosol, do not seem to be saturated by 1#{128}16M un- labeled estradiol, and they presumably represent serum albumin. it therefore seems unlikely that a fetal-specific estradiol-binding protein, comparable to rat alphafetoprotein, is present in fetal guinea pig brain or plasma, and the problem of how fetal guinea pig tissues might be protected against circulating endogenous estrogens remains unresolved.