OESTROGEN METABOLISM IN THE HUMAN FOETUS

Abstract

ABSTRACT In vitro and in vivo experiments were carried out in order to test a previously advanced hypothesis according to which the human foetus is capable of carrying out oestrogen conjugation reactions. In vitro incubation of slices of different foetal tissues with oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) resulted in a significantly increased concentration of conjugated oestriol in foetal 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 foetal tissues were incubated in the absence of oestriol. Countercurrent distribution studies of the conjugated material formed in vitro suggest that it might be identical with oestriol Intra-amniotic injection of 17β-estradiol ((oestra-1,3,5(10))-triene-3,17βdiol) or oestriol to volunteers in whom the foetus was previously separated in situ from its placental connections resulted in a significantly elevated concentration of conjugated oestrone ((3-hydroxy-oestra-1,3,5(10)-trien17-one). 17β-oestradiol and oestriol, respectively, in the foetal lungs and livers and – following 17β administration – also in the intestines. On the other hand, the concentration of conjugated oestrone, 17β-oestradiol or oestriol in the placental tissue was significantly lower under these conditions than in similarly treated patients with an intact foeto-placental connection. When previable foetuses were perfused with diluted blood to which 17β-oestradiol, or oestriol was added, a significantly elevated concentration of conjugated oestrone + 17β-oestradiol, and oestriol, respectively, was found in the foetal lungs, liver, intestines, kidneys + adrenals. It is concluded that the human foetus is already an important site of oestrogen conjugation at relatively early stages of gestation. It is suggested that these conjugation processes take place in several foetal organs, such as the lungs, liver, kidneys, adrenals, intestines, and perhaps also other tissues.