Oestrogen conjugation in mid trimester human fetal brain: A possible role in its sexual differentiation

Abstract

Mid-trimester human fetal brain cytosol incubated with [ 3H]-oestradiol gave a radioactive peak on 5% polyacrylamide gels, which migrated with the bromophenol blue marker (anodic peak) and which could be suppressed by the addition of 100 times molar excess of unlabelled ligand to the incubate. This anodic peak could only be destroyed by proteolytic enzymes if they were added at the beginning of the incubation, but not subsequently, indicating that it did not represent a protein-bound oestradiol. Competition studies show that the anodic peak can be suppressed with natural oestrogens and ethinyloestradiol, but not by the synthetic oestrogens, androgens and progestins tested. Butanol extraction of incubates, followed by t.l.c. in a number of systems, indicates that both oestrone and oestradiol are sulphated. The parent steroids could be liberated by hydrolysis of incubates with either 1N sulphuric acid or aryl sulphatase. This conjugation may effectively curtail the action in fetal tissues of high levels of oestrogens and hence play a role in brain sexual differentation in the human.