OESTROGEN METABOLISM IN THE HUMAN FOETUS

Abstract

In vitro and in vivo experiments were carried out to test a previously advanced hypothesis in which the human fetus is capable of carrying out estrogen conjugation reactions. In vitro incubation of slices of different fetal tissues with estriol (estra-1,3, 5(10)-triene-3,16[alpha], 17[beta]-triol) resulted in a significantly increased concentration of conjugated estriol in fetal liver, lungs, kidneys, adrenals, and perhaps also in skeletal muscle. No such increase was found when endometrial or myometrial tissue from an adult subject was incubated under the same experimental conditions, or when fetal tissues were incubated in the absence of estriol. Counter current distribution studies of the conjugated material formed in vitro suggest that it might be identical with estriol-3-sulphate. Intra-amniotic injection of 17[beta]-estradiol (estra-1, 3, 5(10-triene-3,17[beta]-diol) or estriol to volunteers in whom the fetus was previously separated in situ from its placental connections resulted in a significantly elevated concentration of conjugated estrone (3-hydroxy-estra-l,3-5(10-trien-17-one), 17[beta]-estradiol and estriol, respectively, in the fetal lungs and livers and -following 17/3-estradiol administration- also in the intestines. On the other hand, the concentration of conjugated estrone, 17[beta]-estra-diol or estriol in the placental tissue was significantly lower under these conditions than in similarly treated patients with an intact foeto-placental connection. When previable fetuses were perfused with diluted blood to which 17/3-estradiol or estriol was added, a significantly elevated concentration of conjugated estrone + 17/3-estradiol, and estriol, respectively, was found in the fetal lungs, liver, intestines, kidneys and adrenals. It is concluded that the human fetus is already an important site of estrogen conjugation at relatively early stages of gestation. It is suggested that these conjugation processes take place in several fetal organs, such as the lungs, liver, kidneys, adrenals, intestines, and perhaps also other tissues.