Androgen- and estrogen-binding macromolecules in developing mouse brain: biochemical and genetic evidence.

Abstract

Androgen [testosterone, dehydrotestosterone]- and estrogen [estrodiol-17.beta.]-binding macromolecules from the hypothalamus plus preoptic area of 3-4-wk-old mice were detected and partially characterized. These components bind the respective hormones with high affinity (saturating at 4-8 nM) and sediment with rates typical of presumed steroid receptors (4.0-4.5 S in 0.15 M NaCl, 5.0-7.5 S without salt). A 90-95% reduction in androgen binding found in the androgen-insensitivity mutant mouse, testicular feminization (Tfm), provides a genetic control for the specificity of binding. This reduced androgen binding with Tfm/Y mutants and blocking experiments with non-radioactive estradiol [estra-1,3,5(10)-triene-3,17.beta.-diol] and testosterone (17.beta.-hydroxy-4-androsten-3-one) indicate the existence of at least 2 binding components: 1 with high affinity only for estradiol, the other with affinity for both androgens and estrogens. Based on these properties, a receptor mechanism that detects relative concentrations of androgens and estrogens is proposed.